DETAILED ACTION
Claim Rejections - 35 USC § 102/103
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.
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 1-4, 8, 9, 13 and 16 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Parameswaran (US 20170015968).
With respect to claim 1, Parameswaran discloses a bioreactor comprising a shell (Figure 4B:150) defined by one or more walls and a length and a plurality of porous hollow fiber membranes (Figure 4B:110) inside the shell. This taught in paragraphs [0032]-[0043]. Figure 4B shows that the porous hollow fiber membranes do not span the entire length of the shell. As shown by Fig. 4B, a first end of the porous hollow fiber membranes are connected to a first port for introducing gas (“the plurality of hollow fiber membranes 110 are coupled to one or more modules 170 defining at least one gas inlet and at least one conduit for delivering the gaseous substrate to lumen 112 of membranes 110”). A second end of the porous hollow fiber membranes are fluidically and/or indirectly connected to second ports that receive a processed medium.
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In the event that a fluidic or indirect connection does not read on the claim, it would have been obvious to at least modify the recycle loop shown by Parameswaran so that a second port on the shell is immediately connected to the end of each porous hollow fiber membrane.
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The recycle line 126 is described as providing a simple recirculation function to allow repeated processing of medium through the hollow fibers (“A re-circulating liquid conduit 125, 126 can re-circulate medium 120 through vessel 150”). Those of ordinary skill would have recognized that the same recycling function would be achieved when the end of each hollow fiber membranes is immediately connected to a recycling port (as depicted in the annotated Figure above). A mere rearrangement of parts (here, moving the recycling port on the shell to more directly communicate with the end of each hollow fiber membrane) or duplication of parts (here, providing an additional recycling loop port that more directly communicate with the end of each hollow fiber membrane) that produces a negligible change in device operation is generally considered to be prima facie obvious. See MPEP 2144.04.
With respect to claim 2, Parameswaran discloses the apparatus as described above. Parameswaran shows in Fig. 4B that approximately 50% of the length of the shell remains unoccupied by the plurality of porous hollow fiber membranes.
With respect to claims 3 and 4, Parameswaran discloses the apparatus as described above. Parameswaran shows in Figs. 3 and 4a show that the porous hollow fiber membranes 110 are incorporated into a module (Figure 3:170). A first end of each hollow fiber is potted at a first portion of the module, and a second end of each hollow fiber is potted at a second portion of the module. As previously discussed, Fig. 4B shows that the module and hollow fibers extend to the middle of the bioreactor shell 150. Paragraph [0045] states that the porous hollow fiber membranes may include polypropylene materials.
With respect to claims 8 and 9, Parameswaran discloses the apparatus as described above. Parameswaran depicts in Figs. 4B and %a-5C that the porous hollow fiber membranes are cylindrical tube bundles, and that the shell has the shape of a cylinder.
With respect to claim 13, Parameswaran discloses the apparatus as described above. Parameswaran states that microorganisms are grown on outer surfaces of the porous hollow fiber membranes. See paragraph [0018] (“a biofilm disposed on the outer surface of the hollow fiber membrane”).
With respect to claim 16, Parameswaran discloses the apparatus as described above. Parameswaran teaches a corresponding method for extracting compounds from a broth. Parameswaran states that microorganisms are cultured on outer surfaces of the hollow fiber membranes so that they are in direct contact with a shell side stream containing the broth.
Claims 11 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Parameswaran (US 20170015968) as applied to claims 1 and 13, and further in view of Kasuto (US 20150232797).
Parameswaran discloses the apparatus as described above, however does not teach the use of biocarriers.
Kasuto discloses a bioreactor comprising a plurality of biocarriers (Figure 1A:10) comprising pores for supporting cell growth. See paragraph [0061] (“the material used to produce any of the devices describe herein can…have a hollow or porous interior”). Paragraph [0076] teaches that the biocarriers are configured to be utilized within hollow fiber bioreactors.
Before the effective filing date of the claimed invention, it would have been obvious to support microorganism growth within the pore spaces of a plurality of biocarriers disposed within the shell volume of the Parameswaran reactor. Kasuto teaches that this would increase the surface area for cell attachment and facilitate the formation of cell biofilms. Kasuto further states that the provision of biocarriers improves cell recovery and product purification, which enables commercial up-scaling.
Claims 17, 21-25 and 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Parameswaran (US 20170015968) as applied to claims 1 and 13, and further in view of Kipp (US 20120184759) and Angenent (US 20140322772).
With respect to claim 17, Parameswaran discloses the method described above. Parameswaran teaches that chemical fuel products and precursors (e.g., carboxylates) are purified from the shell side broth using an extraction process. Parameswaran, however, does not appear to teach that the shell side stream of broth flows in a cross-current or co-current pattern in relation to a solvent flowing axially through the plurality of porous hollow fiber membranes.
Kipp discloses a method of extracting one or more compounds from a broth (Figure 1:102). The broth containing microorganisms flows in a counter-current pattern relative to the flow of a solvent flowing axially through a plurality of porous hollow fiber membranes (Figure 1:104a-c). This is taught in paragraphs [0058]-[0063].
Angenent discloses a method of producing and extracting carboxylate from a fermentation broth. Angenent teaches that a hollow fiber separation device is configured to permit extraction of carboxylate products across a porous membrane using a mineral oil solvent comprising trioctylphosphine oxide. This is taught in paragraphs [0051], [0075], [0095] and [0100].
Before the effective filing date of the claimed invention, it would have been obvious to pass a solvent through the plurality of hollow fiber membranes taught by Parameswaran for the purpose of extracting a product from the culture broth. As evidenced by Kipp and Angenent, this is an effective way to obtain a purified compound of interest from a cell culture fluid that is particularly well suited for the recovery of carboxylates. Angenent teaches in paragraph [0051] that membrane-based liquid-liquid extraction using a mineral oil stripping solution is a well-known strategy characterized by a high degree of predictability. It is well within the ability of one of ordinary skill to select an art-recognized solution when determining how to extract product compounds from the Parameswaran broth.
With respect to claim 21, Parameswaran, Kipp and Angenent disclose the combination described above. As previously discussed, Angenent states in paragraphs [0051], [0075], [0095] and [0100] that the membrane separation device utilizes a mineral oil solvent comprising trioctylphosphine oxide.
With respect to claims 22-24, Parameswaran, Kipp and Angenent disclose the combination described above. Angenent teaches in paragraph [0051] that a stripping aqueous phase petraction solution is maintained “at pH greater of 8.0 or above” for removal of carboxylates from the solvent. See also paragraph [0095] (“The solvent, which wet the hydrophobic membranes, was pumped at the same rate on the shell side (outside the fibers) of the membrane, counter-flow to the bioreactor liquid. The solvent was constantly recirculated between contact with the bioreactor liquid and the shell side of a second membrane unit, where it contacted an aqueous phase buffered with a 0.5 M borate solution at pH 9. The pH 9 solution was continuously recirculated from a 5-L reservoir where a pH controller maintained the pH by automatic addition of 5M NaOH”).
With respect to claims 25, 27 and 28, Parameswaran, Kipp and Angenent disclose the combination described above. Parameswaran teaches in paragraph [0036] that temperature and pH within the bioreactor are maintained at optimum values based on the type of microorganism in the culture. The vessel is configured to control temperature and pH, and Parameswaran shows in Table 1 different microorganisms that require temperatures between about 25°C and 35°C and a pH between about 5 and 6. Parameswaran teaches that pH may be controlled through the recirculation of gases through the bioreactor. Paragraph [0094] of Angenent discloses an embodiment in which the bioreactor is maintained at a pH of about 5.5 and a temperature of about 30°C. Angenent states that biogas is recirculated through the reactor. Paragraph [0044] indicates that hydraulic retention time may be about 24 hours.
With respect to claim 29, Parameswaran, Kipp and Angenent disclose the combination described above. Angenent states in paragraph [0003] that medium chain carboxylic acids are produced.
Response to Arguments
Applicant's arguments filed 08 April 2026 have been fully considered but they are not persuasive.
Applicant argues that Parameswaran’s hollow fibers 110 terminate within the reactor structure and therefore do not have a second end that is connected to an outlet or port of the shell 150. However, the second end of each hollow fiber is fluidically connected to the outlet ports of the shell, as fluid is permitted to move from the hollow fibers to the outlets. Furthermore, the second of each hollow fiber is indirectly connected to the outlet ports of the shell, as there are intervening structural features that connect the hollow fibers as a whole to all portions of the shell (i.e., the hollow fibers are not floating/suspended within the shell). The claims do not require any specific kind of connection, and the specification does not provide further guidance as to what kind of connection is contemplated by the claim language. Accordingly, the term “is connected” is given its broadest, reasonable meaning to include fluidic connections and indirect connections.
In the alternative, it would have been obvious to modify Parameswaran so that the second end of each hollow fiber is immediately connected to a recycle port provided on the shell. As discussed in the rejection above, this may be achieved simply by moving the location of the recycle loop inlet port so that the recycle loop inlet port is in direct communication with the ends of the hollow fibers. This may also be achieved by providing an additional recycle loop inlet port that is in direct communication with the ends of the hollow fibers. These modifications would allow medium to be repeatedly recycled through the hollow fiber membranes without disrupting or modifying the basic method of operation taught by Parameswaran.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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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/NATHAN A BOWERS/Primary Examiner, Art Unit 1799
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