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 Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-10, 17-18, 20-21 and 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Nakai et al. (US 2019/0322975), in view of Zhou et al. (US 2015/0158907), and Xu et al. (US 2018/0071689).
Regarding claim 1, Nakai teaches an apparatus for extracting constituents from a biological sample for concentrating a desired constituent of the biological sample, the apparatus comprising:
a plurality of membrane stages (refer fig. 4) comprising modules 20 and 30), wherein each of the plurality of membrane stages comprises:
a membrane (refer 24 in module 20 and 34 in module 30) having a first side (supply side), a second side (permeation side), a first end (near inlets 20a, 30a) and a second end (near outlets 20b, 30b), the membrane having a characteristic to selectively permit one or more constituents of the biological sample to pass through the membrane from the first side to the second side while retaining other constituents of the biological sample at the first side (inherent characteristics of a semi-permeable membrane);
an input chamber (supply side space 22 or 32) having an inlet (20a, or 30a) proximate to the first end of the membrane and an outlet (30a or 30b) proximate to the second end of the membrane, the input chamber configured at the first side of the membrane to permit (a) a tangential flow of the biological sample along a first surface of the membrane at the first side from the first end to the second end a plurality of times (refer circulation flow disclosed in fig. 4), and (b) a trans-membrane passing of the one or more constituents of the biological sample from the first side to the second side (abstract, [0065]-[0071], [0074]); and
an output chamber (permeation side 23 or 33) having an outlet (20c or 30c), the output chamber configured at a second surface of the membrane at the second side and configured to receive the one or more constituents of the biological sample that pass through the membrane (Refer fig. 4, fig. 5),
wherein the plurality of membrane stages is serially configured such that a permeate from a first membrane stage of the plurality of membrane stages is input into a subsequent membrane stage of the plurality of membrane stages to isolate a desired passband of constituents of the biological sample (refer fig. 4 disclosing permeate of module 20 is supplied as feed to module 30).
Nakai does not teach that the tangential flow is reciprocating and that permeate from the last membrane stage is collected in a waste chamber.
Zhou teaches an apparatus for processing cell culture, the apparatus comprising a membrane stage (3) having a membrane (12) and a reversible pump (8). Zhou discloses that providing reversible tangential fluid flow across a surface of a cross-flow filter, as opposed to conventional unidirectional open circuit or bidirectional closed circuit filtration systems, provides for increased viable cell density, increased percentage viable cells, increased specific and/or volumetric productivity, increased specific glucose consumption, and decreased filter fouling (refer [0005]). Zhou also discloses that permeate from filter 11 is collected in holding tank 10. Zhou also discloses in [0020] that “In some examples, an open-circuit filtration system can include multiple TFF units, e.g., connected in series and/or in parallel.
It would have been obvious to one of ordinary skill in the art before the effective filing date of invention to modify the apparatus of Nakai to provide reversible/reciprocating tangential flow that provide increased viable cell density, increased percentage viable cells, increased specific and/or volumetric productivity, increased specific glucose consumption, and decreased filter fouling as taught by Zhou. Collecting the permeate from last stage of Nakai into a container/tank would have been an obvious matter of choice to one of ordinary skill in the art because Zhou establishes that it is known in the art.
Modified Nakai does not teach that the outlet chamber comprises a first outlet proximate to the first end and a second outlet proximate to the second end.
Xu teaches a separation device includes a housing defining a input/first chamber (22), an output/second chamber (24), and a separation member (14) disposed therebetween (abstract, fig. 3), wherein the output/second chamber comprises a first outlet proximate to the first end and a second outlet proximate to the second end (refer outlets 26 at either ends of the membrane).
Duplicating an additional outlet in communication with the outlet chamber in the device of modified Nakai would have been obvious to one of ordinary skill in the art because the court held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced, In re Harza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960). Furthermore, US’689 established that it is known in the art to provide outlets at either ends of the membrane in outlet chamber is known in the art.
Regarding claims 2-3, modified Nakai teaches limitations of claim 1 as set forth above. Xu further teaches that filtration membrane may be a track-etched membrane or a fibrous membrane, and may be, more specifically, a polycarbonate track etched (PCTE) membrane. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
Regarding claim 4, modified Nakai teaches limitations of claim 3 as set forth above. Xu further teaches that the characteristic comprises a pore size of a plurality of pores through the membrane from the first surface to the second surface (fig. 4A, 4B).
Regarding claims 5-8, modified Nakai teaches limitations of claim 4 as set forth above. Xu further teaches that the membrane has a pore size of 0.4 µm (refer [0028]), wherein the pore size characteristic of the membrane is substantially uniform for the membrane (Refer [0005]). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Regarding claims 9-10 and 18, modified Nakai teaches limitations of claim 8 as set forth above. Nakai teaches providing a pump (P1) connected to an inlet of module (20) and pump (P2) connected to an outlet of the module (20).
Regarding claim 17, modified Nakai teaches limitations of claim 2 as set forth above. Nakai teaches that tangential flow is recirculating flow in a loop between inlet and outlet (Refer fig. 4 indicating recirculating flow from tank 10 to inlet 20a to outlet 20b to the tank).
Regarding claims 20-21, modified Nakai teaches limitations of claim 2 as set forth above. Nakai teaches providing a pressure source (refer pump P2) coupled to an outlet of the output chamber (space 23).
Regarding claims 27, 28, and 29, modified Nakai teaches limitations of claim 2 as set forth above. Nakai teaches a vessel (10) that is integrated with the separation modules (refer fig. 4). Zhou teaches providing a port conduit (16) with a valve (18) and port (17) connected to input chamber of membrane device (Refer fig. 5). Whether to use port 17 as a supply port to supply liquid or a discharge port to collect a sample would have been an obvious matter of choice to one of ordinary skill in the art. The port 17 is inherently connected to a means to either supply or collect and vessels/containers are well known in the art to be used as means to supply or collect samples/liquids. Nakai further teaches a collection container (41) coupled to the output chamber (23) of the first membrane device (20), wherein the collection container (41) comprises a conduit (57). While features of an apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function. In re Schreiber, 128 F.3d 1473, 1477-78, 44 USPQ2d 1429, 1431-32 (Fed. Cir. 1997). Since the structure of the prior art teaches all structural limitations of the claim, the same is considered capable of meeting the intended use limitations.
Response to Arguments
Applicant's arguments filed 11/05/2025 have been fully considered but they are not persuasive.
Regarding rejection of claim 1 under 35 U.S.C. § 103 as being unpatentable over Nakai et al. (US 2019/0322975), in view of Zhou et al. (US 2015/0158907), and Xu et al. (US 2018/0071689), applicant argued:
“Contrary to what is claimed, Nakai returns the permeate from its second filter part 30 to the culture vessel. Nakai at [0056]. Thus, Nakai contemplates recombining retentate from the first filter part with permeate from the second filter part. Nakai uses membrane separation because it permits reduced pressure applied to antibodies and suppresses deterioration of the quality thereof. (Id. at [0147]). Zhou does not suggest that its reciprocal flow will suppress antibody deterioration and therefore there is no suggestion in either reference that Zhou is compatible with Nakai's objectives.”
This is not found to be persuasive because Zhou discloses that providing reversible tangential fluid flow across a surface of a cross-flow filter reducing fouling and improves filter performance (refer [0004], [0005], [0006]). Therefore, one of ordinary skill in the art would have found it beneficial to use reversible fluid flow across a surface of filter in the system of Nakai.
Applicant further argued:
“Applicant submits that Nakai, with its multiple filter parts outside of the reactor, is contrary to the objectives of Zhou, which seeks to decrease the amount of time the culture is outside of the reactor. Applicant submits that the skilled person would not modify Nakai 's perfusion system with Zhou 's reciprocal flow because that would only increase the amount of time that the culture would be outside the bioreactor, which is completely contrary to Zhou 's objectives.”
This is not found to be persuasive because Zhou’s filter unit 11 is also outside the reactor similar to Nakai’s filter units 20 and 30. Zhou also discloses in [0020] that “In some examples, an open-circuit filtration system can include multiple TFF units, e.g., connected in series and/or in parallel. For example, a system that includes two or more TFF units can include fluid conduits fluidly connecting neighboring pairs of TFF units in the system. In other examples, a system can include two or more sets of two or more TFF units fluidly connected by fluid conduits.” suggesting a plurality of TFF units connected in series or parallel which would obviously increase amount of time required to process the cell culture.
Applicant further argued:
“Applicant also notes that the perfusion system in Nakai returns the permeate from the last stage to the bioreactor, since Nakai is concerned with extracting antibodies from the culture. Thus, the perfusion systems of Nakai and Zhou have a distinctly different objective than the currently claimed apparatus.”
This is not found to be persuasive because whether to return the permeate of second stage or discard/collect in a separate container would have been an obvious matter of choice to one of ordinary skill in the art because Zhou discloses collecting permeate in a container.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/PRANAV N PATEL/Primary Examiner, Art Unit 1777