DETAILED CORRESPONDENCE
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 .
Response to Amendment
Based on the amended claims and remarks, received on 9/3/26, the previous prior art rejections have been withdrawn and modified to address the claim amendments.
Claim Status
Claims 1, 3-17 are pending with claims 1, 3-6, 16, 17 being examined and claims 7-15 deemed withdrawn.
Claim Rejections - 35 USC § 103
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 4-5, 16, 17 are rejected under 35 U.S.C. 103 as being unpatentable over Tachibana et al (US 20160199840; hereinafter “Tachibana”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”; already of record) in view of Stahl et al (US 20190224675; hereinafter “Stahl”).
As to claim 1, Tachibana teaches a method, comprising: receiving at a first end of a channel of a microfluidic device, a biologic sample including a nucleic acid, the channel disposed along a planar surface within the microfluidic device; warming a first subset of a plurality of heating elements disposed adjacent to the channel of the microfluidic device to a first particular temperature of a particular warming and cooling protocol and a second subset of the plurality of heating elements disposed adjacent to the channel of the microfluidic device to a second particular temperature of the particular warming and cooling protocol, the warming and cooling protocol associated with amplification of the nucleic acid; moving the biologic sample from the first end of the channel to a second end of the channel opposite the first end at a flow rate that is adjusted according to the warming and cooling protocol, and the biologic sample is disposed adjacent to the first and second subsets of heating elements for a corresponding amount of time, the corresponding amount of time for each respective subset determined according to a defined sequence of temperatures of the warming and cooling protocol; and intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements while the biologic sample moves from the first end of the channel to the second end of the channel (Tachibana teaches introducing a nucleic acid into a microchannel where there are different subsets of heaters 141/142 to warm the sample; [95, 97, 102, 103, 115-123], Fig. 5. Tachibana teaches that feed velocity of the sample/fluid is determined by pressure loss, which is the primary contributor to the feed velocity, and also that pressure loss is based on temperature; [174, 187]. Tachibana teaches in Fig. 11 that at 95 C that the pressure loss is less, due to increased heat and lower viscosity, so the feed velocity at a pressure loss of .4 is around 15 mm/s, while the feed velocity at a pressure loss of .4 at 60 C is around 7.5 mm/s. Therefore, Tachibana teaches that as the temperature increases that the feed velocity is increased/adjusted, and that as the temperature decreases that the feed velocity is decreased/adjusted. Tachibana also teaches adjusting the feed velocity; [328]. In Tachibana, adjusting the feed velocity (flow rate) based on temperature (which is related to pressure loss) would mean that the flow rate is adjusted based on temperature. The warming and cooling protocol have not been defined and because the prior art teaches adjusting flow rates at specific temperatures, then this is sufficient to serve as the warming and cooling protocol until further defined).
Although Tachibana teaches that the flow rate/velocity can change, Tachibana does not teach adjusting the flow rate. However, Ikeda teaches the analogous art of a method for adjusting the temperature using various heaters in a microfluidic channel (Ikeda; abstract, Fig. 1, 2, 4-6) where the flow rate is known to be adjusted based on the nucleic acid length, the nucleic acid reaction rate, and other parameters, including temperature (Ikeda; [40]. Ikeda teaches that increasing flow rate can decrease the time at specific temperature zones and that specific temperature zones need differing times to perform the reactions; [54]. Ikeda teaches that flow rate and channel size can be controlled, because these parameters relate to the rection rate; [40]. Ikeda discloses that when subjecting samples to PCR that reaction times and temperatures are controlled so that the required reaction takes place [5, 23] (see also Fig. 2), and that the time for which the fluid flows may depend on the length of the channel [9, 50, 52]. Ikeda also discloses that it is known in the art to control the temperature and rate in order to achieve the required time for reactions [10].). Thus, with respect to adjusting the flow rate during PCR, it would have been obvious to a person having ordinary skill in the art to modify Tachibana’s sample flow rate to be adjusted as in Ikeda because Ikeda teaches that it is known to adjust the flow rate (Ikeda; [40]) and because Ikeda teaches that adjusting flow rate based on time at specific temperatures helps to ensure that samples are at the specific temperatures for the required time for reactions to take place (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2). Ikeda teaches that flow rate is known to be adjusted based on the nucleic acid length, the nucleic acid reaction rate, and other parameters including channel length (Ikeda; [40]) and also that different reactions require different times (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2). Therefore, it is evident that Ikeda recognizes that the flow rate is a result effective variable, and it would have been obvious to optimize Tachibana’s flow rate to be adjusted as in Ikeda depending on the nucleic acid length, the nucleic acid reaction rate, and other parameters as taught by Ikeda (Ikeda; [40]) and also to adjust the flow rates to ensure the samples were at the required temperature stage for the necessary time for the reaction to take place (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2). This modification would also result in the biologic samples each disposed adjacent to the heaters for a corresponding amount of time defined by the warming and cooling protocol.
Modified Tachibana does not specifically teach that the flow rate is adjusted by a controller. However, Stahl teaches the analogous art of moving samples through a microfluidic device, where it is known that valves and other external controls are obvious and known techniques that control and vary flow rate (Stahl; [142]) where the fluid flow components are controlled by a valve driver or controller/computer (Stahl; [233, 238, 244]). It would have been obvious to one of ordinary skill in the art to have modified the adjustment of the flow rate in the microfluidic device of modified Tachibana to have been adjusted via a controller and valves as in Stahl because Stahl teaches that valves and other external controls are obvious and known techniques that control and vary flow rate (Stahl; [142]).
As to claim 4, modified Tachibana teaches the method of claim 1, including: warming the second subset of the plurality of heating elements to the second particular temperature of the particular warming and cooling protocol; and not warming a third set of elements disposed adjacent to the channel of the microfluidic device, the third set of elements associated with cooling zones of the microfluidic device (Tachibana teaches different subsets of heaters 141/142 to warm the sample; [95, 97, 102, 103, 115-123], Fig. 5. Tachibana does not teach the heaters are warming to a different temperature, so the heaters 141 on the left are the first subset and the heaters 141 on the right are the second subset, whereby the heaters 142 serve to cool; [131]. Alternatively, the heaters 141 on the left are the first subset and the heaters 142 on the left are the second subset, and the heaters 142 on the right are the third subset and serve to cool; [131]. Tachibana teaches a temperature control; Fig. 3, [204]).
As to claim 5, modified Tachibana teaches the method of claim 4, including digitally controlling and monitoring the temperature of the plurality of heating elements (Tachibana teaches a temperature control; Fig. 3, [121, 200, 204]).
As to claim 16, modified Tachibana teaches the method of claim 1, comprising adjusting the flow rate of the biologic sample according to the warming and cooling protocol by: adjusting the flow rate of the biologic sample according to a defined sequence of temperatures and a corresponding amount of time at which the biologic sample is held at a particular temperature in the sequence (The modification of the adjusting of the flow rate during PCR of Tachibana to have been adjusted based on time and reaction rates/temperatures as in Ikeda have already been discussed above. Ikeda; [40]. Ikeda teaches that increasing flow rate can decrease the time at specific temperature zones and that specific temperature zones need differing times to perform the reactions; [54]. Ikeda teaches that flow rate and channel size can be controlled, because these parameters relate to the rection rate; [40]. Ikeda discloses that when subjecting samples to PCR that reaction times and temperatures are controlled so that the required reaction takes place [5, 23] (see also Fig. 2), and that the time for which the fluid flows may depend on the length of the channel [9, 50, 52]. Ikeda also discloses that it is known in the art to control the temperature and rate in order to achieve the required time for reactions [10]. Alternatively, the modification of the adjustment of the flow rate in the microfluidic device of modified Tachibana to have been adjusted via a controller and valves as in Stahl has already been discussed above. Stahl; [142] & see claim 1 above).
As to claim 17, modified Tachibana teaches the method of claim 1, wherein the flow rate is adjusted by actuating a plurality of valves to control a flow of the biologic sample through the channel, the plurality of valves actuated by circuitry in a controlled manner consistent with the warming and cooling protocol (The modification of the adjustment of the flow rate in the microfluidic device of modified Tachibana to have been adjusted via a controller and valves as in Stahl has already been discussed above. Stahl; [142] & see claim 1 above).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Tachibana et al (US 20160199840; hereinafter “Tachibana”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”; already of record) in view of in view of Stahl et al (US 20190224675; hereinafter “Stahl”) in view of Gale et al (US 20100167288; hereinafter “Gale”; already of record).
As to claim 3, modified Tachibana teaches the method of claim 1, and intermittently cooling, according to the particular warming and cooling protocol, the biologic sample.
Modified Tachibana does not specifically teach cooling using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel. However, Gale teaches the analogous art of microfluidics that are heated and cooled for PCR, and using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel (Gale teaches cooling fins with cooling air that flows through; Fig. 1, [66]. Alternatively, Gale teaches water or forced fluid, or a refrigeration coil; [66]). It would have been obvious to one of ordinary skill in the art to have cooled the device of modified Tachibana using the cooling elements of Gale because Gale teaches that the cooling elements help to better cool the device to remove heat (Gale; [66]), and that there are various obvious ways to extract heat from the PCR device (Gale; [66]).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Tachibana et al (US 20160199840; hereinafter “Tachibana”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”) in view of in view of Stahl et al (US 20190224675; hereinafter “Stahl”) in view of Wilding et al (WO93/22053; hereinafter “Wilding”; already of record).
As to claim 6, modified Tachibana teaches the method of claim 1, where the microfluidic device includes a first region with a plurality of heating elements and a second region including a plurality of heating elements, and where wherein intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements includes cycling the biologic sample between the first region and the second region a specified number of times according to the warming and cooling protocol (Tachibana teaches moving the sample between the heating regions; see claim 1 above).
Modified Tachibana does not specifically teach the different heating regions are chambers in which the sample is cycled between. However, Wilding teaches the analogous art of PCR in a microfluidic channel where the sample is cycled between various chambers at different temperatures (Wilding; Fig. 15, p. 32). It would have been obvious to one of ordinary skill in the art have modified the heating regions of modified Tachibana to be chambers as in Wilding because Wilding teaches that the chambers help to accommodate solution for cycling during PCR (Wilding; Fig. 15, p. 32).
Claims 1, 4-5, 16, 17 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al (US 20100021972; hereinafter “Cho”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”; already of record) in view of Klein et al (US 20210131989; hereinafter “Kelin”).
As to claim 1, Cho teaches a method, comprising: receiving at a first end of a channel of a microfluidic device, a biologic sample including a nucleic acid, the channel disposed along a planar surface within the microfluidic device; warming a first subset of a plurality of heating elements disposed adjacent to the channel of the microfluidic device to a first particular temperature of a particular warming and cooling protocol and a second subset of the plurality of heating elements disposed adjacent to the channel of the microfluidic device to a second particular temperature of the particular warming and cooling protocol, the warming and cooling protocol associated with amplification of the nucleic acid; moving the biologic sample from the first end of the channel to a second end of the channel opposite the first end at a flow rate that is adjusted according to the warming and cooling protocol, and the biologic sample is disposed adjacent to the first and second subsets of heating elements for a corresponding amount of time, the corresponding amount of time for each respective subset determined according to a defined sequence of temperatures of the warming and cooling protocol; and intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements while the biologic sample moves from the first end of the channel to the second end of the channel (Cho teaches introducing nucleic acid into inlet, and flowing solution in channel 130, and multiple heaters in each region; [100, 105-108], Fig. 7. Cho teaches multiple heaters in each region; [74, 100, 105-108], Fig. 7. Cho teaches that the reaction rate is based on the flow rate; [13]. Cho also teaches that the flow rate of the input fluid, which interacts with the sample, is adjusted; [88, 91, 126]. Therefore, the fluid and corresponding sample have the flow rate adjusted such that the sample is associated with heating elements for defined times, as any time would be a defined time period. Additionally, standard samples are diluted to various concentrations and their flow rates are adjusted. In this respect, the standard sample that is created, with an adjusted flow rate is still considered a biologic sample. Because the reaction rate is based on the flow rate, and because Cho is performing defined PCR reactions at specific temperatures, then the reaction rate (and time) at specific temperatures would be related to and controlled by the flow rate, which Cho teaches as adjusting. The warming and cooling protocol have not been defined and because the prior art teaches adjusting flow rates at specific temperatures, then this is sufficient to serve as the warming and cooling protocol until further defined).
Although Cho teaches that the flow rate/velocity can change, Cho does not teach adjusting the flow rate. However, Ikeda teaches the analogous art of a method for adjusting the temperature using various heaters in a microfluidic channel (Ikeda; abstract, Fig. 1, 2, 4-6) where the flow rate is known to be adjusted based on the nucleic acid length, the nucleic acid reaction rate, and other parameters, including temperature (Ikeda; [40]. Ikeda teaches that increasing flow rate can decrease the time at specific temperature zones and that specific temperature zones need differing times to perform the reactions; [54]. Ikeda teaches that flow rate and channel size can be controlled, because these parameters relate to the rection rate; [40]. Ikeda discloses that when subjecting samples to PCR that reaction times and temperatures are controlled so that the required reaction takes place [5, 23] (see also Fig. 2), and that the time for which the fluid flows may depend on the length of the channel [9, 50, 52]. Ikeda also discloses that it is known in the art to control the temperature and rate in order to achieve the required time for reactions [10].). Thus, with respect to adjusting the flow rate during PCR, it would have been obvious to a person having ordinary skill in the art to modify Cho sample flow rate to be adjusted as in Ikeda because Ikeda teaches that it is known to adjust the flow rate (Ikeda; [40]) and because Ikeda teaches that adjusting flow rate based on time at specific temperatures helps to ensure that samples are at the specific temperatures for the required time for reactions to take place (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2). Ikeda teaches that flow rate is known to be adjusted based on the nucleic acid length, the nucleic acid reaction rate, and other parameters including channel length (Ikeda; [40]) and also that different reactions require different times (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2). Therefore, it is evident that Ikeda recognizes that the flow rate is a result effective variable, and it would have been obvious to optimize Cho flow rate to be adjusted as in Ikeda depending on the nucleic acid length, the nucleic acid reaction rate, and other parameters as taught by Ikeda (Ikeda; [40]) and also to adjust the flow rates to ensure the samples were at the required temperature stage for the necessary time for the reaction to take place (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2). This modification would also result in the biologic samples each disposed adjacent to the heaters for a corresponding amount of time defined by the warming and cooling protocol.
Modified Cho does not specifically teach that the flow rate is adjusted by a controller. However, Klein teaches the analogous art of moving samples through a microfluidic device, where the flow rate is controlled by valves and where a controller controls all of the fluidic operations (Klein; [63], Fig. 2C). It would have been obvious to one of ordinary skill in the art to have modified the adjustment of the flow rate in the microfluidic device of modified Cho to have been adjusted via a controller and valves as in Klein because Klein teaches that valves and other external controls are obvious and known techniques that control and vary flow rate (Klein; [63]).
As to claim 4, modified Cho teaches the method of claim 1, including: warming the second subset of the plurality of heating elements to the second particular temperature of the particular warming and cooling protocol; and not warming a third set of elements disposed adjacent to the channel of the microfluidic device, the third set of elements associated with cooling zones of the microfluidic device (Cho teaches three different heating subset regions; [74, 100, 105-108], Fig. 7. Cho teaches that at least one of the heating regions is used to cool; [80, 82, 127, 129]).
As to claim 5, modified Cho teaches the method of claim 4, including digitally controlling and monitoring the temperature of the plurality of heating elements (Cho; [105-108]).
As to claim 16, modified Cho teaches the method of claim 1, comprising adjusting the flow rate of the biologic sample according to the warming and cooling protocol by: adjusting the flow rate of the biologic sample according to a defined sequence of temperatures and a corresponding amount of time at which the biologic sample is held at a particular temperature in the sequence (The modification of the adjusting of the flow rate during PCR of Cho to have been adjusted based on time and reaction rates/temperatures as in Ikeda have already been discussed above. Ikeda; [40]. Ikeda teaches that increasing flow rate can decrease the time at specific temperature zones and that specific temperature zones need differing times to perform the reactions; [54]. Ikeda teaches that flow rate and channel size can be controlled, because these parameters relate to the rection rate; [40]. Ikeda discloses that when subjecting samples to PCR that reaction times and temperatures are controlled so that the required reaction takes place [5, 23] (see also Fig. 2), and that the time for which the fluid flows may depend on the length of the channel [9, 50, 52]. Ikeda also discloses that it is known in the art to control the temperature and rate in order to achieve the required time for reactions [10] Alternatively, the modification of the adjustment of the flow rate in the microfluidic device of modified Cho to have been adjusted via a controller and valves as in Klein has already been discussed above. Klein; [63] & see claim 1 above).
As to claim 17, modified Cho teaches the method of claim 1, wherein the flow rate is adjusted by actuating a plurality of valves to control a flow of the biologic sample through the channel, the plurality of valves actuated by circuitry in a controlled manner consistent with the warming and cooling protocol (The modification of the adjustment of the flow rate in the microfluidic device of modified Cho to have been adjusted via a controller and valves as in Klein has already been discussed above. Klein; [63] & see claim 1 above).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Cho et al (US 20100021972; hereinafter “Cho”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”; already of record) in view of Klein et al (US 20210131989; hereinafter “Kelin”)in view of Beer et al (US 20090226971; hereinafter “Beer”; already of record).
As to claim 3, modified Cho teaches the method of claim 1, and intermittently cooling, according to the particular warming and cooling protocol, the biologic sample.
Modified Cho does not specifically teach cooling using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel. However, Beer teaches the analogous art of microfluidics that are heated and cooled for PCR, and using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel (Beer teaches a cooler and cooling line through which cooling agent flows through; Fig. 1, [18, 38]). It would have been obvious to one of ordinary skill in the art to have cooled the device of modified Cho using the cooling elements of Beer because Beer teaches that the cooling elements help to better cool the device to remove heat (Beer; [38]), and that this helps to save time for temperature changes (Beer; [38]).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Cho et al (US 20100021972; hereinafter “Cho”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”; already of record) in view of Klein et al (US 20210131989; hereinafter “Kelin”)in view of Kornilovich et al (US 20120244604; hereinafter Kornilovich”; already of record).
As to claim 6, modified Cho teaches the method of claim 1, where the microfluidic device includes a first region with a plurality of heating elements and a second region including a plurality of heating elements, and where wherein intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements includes cycling the biologic sample between the first region and the second region a specified number of times according to the warming and cooling protocol (Cho teaches moving the sample between the heating regions; see claim 1 above).
Modified Cho does not specifically teach the different heating regions are chambers in which the sample is cycled between. However, Kornilovich teaches the analogous art of PCR in a microfluidic channel (Kornilovich; [27, 28]) where the sample is cycled between various chambers at different temperatures (Kornilovich; Fig. 2-4, [37-40]). It would have been obvious to one of ordinary skill in the art have modified the heating regions of modified Cho to be chambers as in Kornilovich because Kornilovich teaches that the chambers help to accommodate solution for cycling during PCR (Kornilovich; Fig. 2-4, [37-40]).
Response to Arguments
Applicant’s arguments filed on 9/3/26 have been considered, but they are not persuasive as they are towards the amended claims and not the current ground of rejection.
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.
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/BENJAMIN R WHATLEY/Primary Examiner, Art Unit 1798
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