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
Claims 10-22 and 24-35 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims 10-22 and 24-35 have not been further treated on the merits.
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 1-3,5,7, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Ballermann et al. (US 5,843,781) and further in view of Hilt et al. (“Transcytosis of the Polymeric Ig Receptor Requires Phosphorylation of Serine 664 in the Absence but Not the Presence of Dimeric IgA” 1993).
Regarding claim 1 Ballerman discloses a bioreactor construct comprising a cell monolayer in contact with a surface of a plurality of hollow capillary tubes arranged in a parallel array within a tubular cartridge defining an intracapillary (IC) space and an extracapillary (EC) space of the bioreactor, each hollow capillary tube constructed of a semi-permeable membrane defining an internal surface adjacent to the IC space and an external surface adjacent to the EC space, wherein the cell monolayer is in contact with the internal or external surface of the plurality of capillary tubes and wherein a cell culture medium fills the IC space or the EC space, or both. (See Ballerman Abstract and Figs. 1a-1c, Col. 6 lines 4-30, wherein a bioreactor comprises a plurality of a hollow fiber formed from a semi-permeable membranes such that an IC and EC space is formed wherein a cell monolayer is formed on the IC space and culture medium fills the IC space to culture the cells.)
Ballermann discloses all the claim limitations as set forth above as well as the device may be used to various known co-cultures but does not specifically disclose seeded antibody secreting cells and monolayer cells.
Hirt discloses a co-culture of antibody secreting hybridoma cells and a cell epithelial cell monolayer. (See Abstract and Figure 1 wherein epithelial cells are co-cultured with antibody secreting hybridoma cells in across a semi-permeable filter.)
It would have been obvious to one of ordinary skill in the art at the time of filing to provide a epithelial cell monolayer and antibody secreting hybridoma cell co-culture as described by Hirt et al. in the device of Ballermann because such a co-culture is known to be studied and fulfills the need for cells which are to be studied as described by Ballermann and such a system allows for the more in-vivo like study of such cells as would be desirable in Ballermann.
Regarding claim 2 Ballermann discloses all the claim limitations as set forth above as well as the device wherein the internal or external surface of the plurality of capillary tubes is coated with one or more extracellular matrix components and the cell monolayer is in contact with the coated surface. (See Ballermann Col. 5 Lines 20-30 wherein ECM materials are used to coat the surface of the hollow capillary tubes which the cell monolayer is in contact with.)
Regarding claim 3 Ballermann discloses all the claim limitations as set forth above as well as the device wherein the one or more extracellular matrix components is selected from the group consisting of collagen IV, laminin, entactin, tenascin, and fibronectin. (See Ballermann Col. 5 Lines 20-30 wherein laminin and fibronectin are used to coat the surface of the hollow capillary tubes.)
Regarding claims 5 and 7 Ballermann discloses all the claim limitations as set forth above as well as the device wherein the internal or external surface of the plurality of capillary tubes is coated with one or more of a natural polymer. (See Ballermann Col. 5 Lines 20-30 wherein the internal surface of the tubes is coated with collagen, i.e. a natural polymer.)
Regarding claim 23 Ballermann discloses a method for culturing a co culture of cells the method comprising seeding a bioreactor construct with a first type of cells and a second type of cells; wherein the bioreactor construct comprises a surface of a plurality of hollow capillary tubes arranged in a parallel array within a tubular cartridge defining an intracapillary (IC) space and an extracapillary (EC) space of the bioreactor, each hollow capillary tube constructed of a semi-permeable membrane defining an internal surface adjacent to the IC space and an external surface adjacent to the EC space; wherein the second cell type forms a monolayer in contact with the internal or external surface of the plurality of capillary tubes; and wherein a cell culture medium fills the IC space or the EC space, or both. (See Ballerman Abstract and Figs. 1a-1c, Col. 6 lines 4-30, wherein a method of growing a co-culture of cells first and second cell types which 3uses a bioreactor comprising a plurality of a hollow fiber formed from a semi-permeable membranes such that an IC and EC space is formed wherein a cell monolayer is formed on the IC space and culture medium fills the IC space to culture the cells.)
Ballermann discloses all the claim limitations as set forth above as well as the method may be used with various known co-cultures but does not specifically disclose seeded antibody secreting cells and epithelial monolayer cells.
Hirt discloses a co-culture of antibody secreting hybridoma cells and a cell epithelial cell monolayer. (See Abstract and Figure 1 wherein epithelial cells are co-cultured with antibody secreting hybridoma cells in across a semi-permeable filter.)
It would have been obvious to one of ordinary skill in the art at the time of filing to provide a epithelial cell monolayer and antibody secreting hybridoma cell co-culture as described by Hirt et al. in the method of Ballermann because such a co-culture is known to be studied and fulfills the need for cells which are to be studied as described by Ballermann and such a system allows for the more in-vivo like study of such cells as would be desirable in Ballermann.
Claims 4,6, and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Ballermann et al. (US 5,843,781) in view of Hilt et al. (“Transcytosis of the Polymeric Ig Receptor Requires Phosphorylation of Serine 664 in the Absence but Not the Presence of Dimeric IgA” 1993) as applied to claims above, and further in view of Sivakumaran (US 2018/0298343).
Regarding claim 4 Ballermann discloses all the claim limitations as set forth above as well as the device wherein the surface of each hollow capillary tube is coated with ECM materials and said materials collagen and laminin. (See Ballermann Col. 5 Lines 20-30 wherein laminin and collagen are used to coat the surface of the hollow capillary tubes.)
In regards to utilizing both collagen and laminin it is noted that such a modification would have required combining two products known for the same purpose, i.e. cell culture, which would have been obvious to one of ordinary skill in the art at the time of filing because it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Furthermore in regards to the collagen being collagen IV and the laminin being laminin 1 it is noted that such are know forms of hollow fiber coatings for use in cell culture as described by Sivakumaran (See Sivakumaran [0145]- [0146] wherein collagen IV and/or laminin 1 are used to coat the surface of the hollow capillary tubes.) It would have been obvious to one of ordinary skill in the art at the time of filing to utilizer the specific collagen IV and laminin 1 as described by Sivakumaran in the device of Ballermann because such are known and specific forms of collagen and laminin used in ECM coatings for the effective and biocompatible growth of cells as would be desirable in Ballermann and one would have a reasonable expectation of success in utilizing such specific forms of collagen and laminin.
Regarding claim 6 Ballermann discloses all the claim limitations as set forth above as well as the device wherein other coatings may be used but does not specifically disclose wherein the natural polymer is selected from the group consisting of agarose, alginate, cellulose, chitosan, gelatin, and mixtures thereof.
Sivakumaran discloses a hollow fiber capillary tube bioreactor for cell co-culture wherein the internal or external surface of the plurality of capillary tubes is coated with one or more of a natural polymer, a biocompatible synthetic polymer, a synthetic peptide, or a composite derived from any combination thereof and wherein the natural polymer is selected from the group consisting of agarose, alginate, cellulose, chitosan, gelatin, and mixtures thereof. (See Sivakumaran [0137]wherein the hollow capillary tubes are coated with natural polymer gelatin.)
It would have been obvious to one of ordinary skill in the art at the time of invention to utilize gelatin as a coating as described by Sivakumaren in the device of Ballermann because such a coating is a known hollow fiber coating material which allows the biocompatible culture of cells as would be desirable in Ballermann nd one of ordinary skill in the art would have a reasonable expectation of success in utilizing such an equivalent coating in the device of Ballermann.
Regarding claims 8-9 Ballermann discloses all the claim limitations as set forth above as well as the device wherein the semi-permeable membrane may be formed from various biocompatible materials but does not disclose the specifics or porosity thereof.
Sivakumaran discloses a hollow fiber capillary tube bioreactor for cell co-culture wherein the semi-permeable membrane forming the hollow fibers is fabricated from polyvinylidene difluoride (PVDF) or polysulfone. (See Sivakumaran [0131] wherein the semi-permeable membrane forming the hollow fibers is from polyvinylidene difluoride (PVDF) or polysulfone among other materials.) and wherein the semi-permeable membrane has a molecular weight cut-off (MWCO) between 5-80 kilodaltons (kDa). (See Sivakumaran [0126] wherein a MWCO of 65 kDA is used for the semi-permeable membrane.)
It would have been obvious to one of ordinary skill in the art at the time of invention to utilize semi-permeable membrane formed of the materials and having a permeability described by Sivakumaren in the device of Ballermann because such hollow fibers allow for the biocompatible growth of cells as well as allow the effective transfer of nutrients and waste so cells may be efficiently grow as would be desirable in Ballermann and one of ordinary skill in the art would have a reasonable expectation of success in utilizing such an material the device of Ballermann
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONATHAN M HURST whose telephone number is (571)270-7065. The examiner can normally be reached on M-F 7AM-4PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached on 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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/JONATHAN M HURST/ Primary Examiner, Art Unit 1799