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 .
In view of the Petition Decision filed 07/23/2026, Applicant's request filed 05/05/2026 for reconsideration of the finality of the rejection of the last Office action (i.e. Final Rejection filed 04/28/2026) is persuasive and, therefore, the finality of that action is withdrawn.
Response to Amendment
The Amendment filed 03/30/2026 has been entered. Claims 37-40, 44, and 46-55 remain pending in the application. Claims 38, 40, and 55 are withdrawn.
Applicant’s amendments to the claims and drawings have overcome each and every objection and 112(b) rejections previously set forth in the Non-Final Office Action mailed 10/24/2025.
Claim Objections
Claim 52 is objected to because of the following informalities: In line 2, it is suggested to recite “comprises comprising” as “comprises” or “comprising”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 37, 39, 44, and 46-54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 37, claim 37 recites “two second inlet channels…are each from 0.8mm to 0.12mm wide”. While the specification discloses inlet channels for the second fluid are 0.08 to 0.12 mm wide (page 8, lines 34-36), the disclosure fails to recite the two second inlet channels are from 0.8mm to 0.12mm wide. Therefore, the claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims 39, 44, and 46-54 are rejected by virtue of their dependency on claim 37.
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.
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.
Claims 37, 39, 44, and 46-52 are rejected under 35 U.S.C. 103 as being unpatentable over Harvengt et al. (WO 2018219521 A1; cited in the IDS filed 08/27/2024) in view of Fu et al. (CN 1542429 A; see machine translation).
Regarding claim 37, Harvengt teaches a method of manufacturing a liposomal adjuvant using a microfluidic device (page 5, lines 35-36; Fig. 1),
the microfluidic mixing device (Fig. 1; pages 7-10) comprising:
(i) a mixing chamber (Fig. 1; page 7, “mixing chamber”);
(ii) one first inlet channel (Fig. 1 and page 8, second paragraph, teaches at least one inlet for delivery of a first solution; page 9, fourth paragraph), which is into the mixing chamber (page 8, second paragraph);
(iii) two second inlet channels (Fig. 1 and page 8, third paragraph, teaches two inlets for delivery of a second solution; page 9, fourth paragraph), which are into the mixing chamber (page 8, third paragraph) and are each from 0.8 mm to 0.12 mm wide (page 32, lines 27-28, teaches the inlets are 0.2 mm wide, which is within the range of 0.8 mm to 0.12 mm, i.e. 0.12mm-0.80mm);
(iv) an outlet (Fig. 1 and page 8, last paragraph; page 9, fourth paragraph), which is from the mixing chamber (Fig. 1 and page 8, last paragraph);
wherein:
the one first inlet channel and two second inlet channels are disposed substantially symmetrically at a proximal end of the mixing chamber (Fig. 1 and page 9, fourth paragraph) and the outlet is at a distal end of the mixing chamber (Fig. 1 and page 9, fourth paragraph);
the method comprising:
(a) mixing in the device mixing chamber a first solution and a second solution, thereby obtaining a mixed material comprising the liposomal adjuvant (page 6, lines 1-2, teaches mixing in the device a first solution comprising a solvent, phosphatidylcholine lipid and a sterol, and a second solution comprising water and the saponin, therefore comprises a mixed material comprising a liposomal adjuvant; page 15 teaches mixing of the first and second solutions in the mixing chamber; page 16 teaches upon mixing of the first and second solutions, liposomes will form), the first solution being delivered into the mixing chamber by the one first inlet channel (page 8, second paragraph; page 9, fourth paragraph) and comprising a solvent and a lipid (page 6, lines 1-2, “solvent, phosphatidylcholine lipid and a sterol”), the second solution comprising water (page 6, lines 1-2) and being delivered into the mixing chamber by the two second inlet channels (page 8, third paragraph; page 9, fourth paragraph), the mixed material exiting the mixing chamber by the outlet (page 8, last paragraph teaches an outlet for recover of the mixed material, therefore mixed materials exits the mixing chamber by the outlet); and
(b) removing the solvent from the mixed material (page 6, line 3).
While Harvengt teaches the desire to facilitate adequate mixing (page 8, lines 13-14), Harvengt fails to teach: the mixing chamber comprising a baffle.
Fu teaches a microfluidic chemical analysis system device comprising a cross-flow-guiding micro static mixer (paragraph [0002]; Figs. 1-5). Fu teaches purpose of mixing is to reduce heterogeneity, for example for dilution, or to enhance the rate of chemical reactions, so it is very important to achieve fast and efficient mixing (paragraph [0004]). Fu teaches the device comprises a mixing chamber (Figs. 1-3, elements 6 and 7) and the mixing chamber includes baffles (Figs. 1-3, guide blocks 4, 4’, 5, 5’). Fu teaches the invention has the following beneficial effects: by arranging alternating guide blocks in the pipeline, shear flow and extension flow can be generated in the flow field, the interface area between different fluids is increased, the molecular diffusion effect is enhanced, and ultimately uniform mixing at the molecular level is achieved (paragraph [0013]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the mixing chamber of Harvengt to incorporate the teachings of microfluidic devices comprising a mixing chamber with baffles of Fu (Figs. 1-3; paragraph [0013]) to provide: the mixing chamber comprising a baffle. Doing so would have a reasonable expectation of successfully improving mixing as taught by Fu (paragraph [0013]).
Regarding claim 39, Harvengt further teaches the method of claim 37 further comprising: (c) mixing the liposomal adjuvant with an immunogen, or a polynucleotide encoding the immunogen (page 24, lines 1-3).
Regarding claim 44, Harvengt further teaches wherein the first inlet channel is from 0.1 mm to 0.7 mm wide (page 32, lines 27-28, teaches the inlets are 0.2 mm wide).
Regarding claim 46, Harvengt further teaches wherein each of the directions of flow from the one first inlet channels and the two second inlet channels into the mixing chamber are substantially parallel to the general direction of flow in the mixing chamber (page 8, lines 32-35).
Regarding claim 47, Harvengt further teaches wherein the mixing chamber has a length from 15 mm to 100 mm (page 9, lines 8-9 teaches the mixing chamber has a length of 1.5-5 cm, i.e. 15-50mm).
Regarding claim 48, Harvengt further teaches wherein the mixing chamber has a maximum width of from 0.8 mm to 2.2 mm (page 39, line 26 teaches the mixing chamber width is 2000um, i.e. 2mm).
Regarding claim 49, Harvengt further teaches wherein the mixing chamber has a minimum width of from 0.8 mm to 2.2 mm (page 39, line 26 teaches the mixing chamber width is 2000um, i.e. 2mm).
Regarding claim 50, Harvengt further teaches wherein the mixing chamber has a depth of from 0.1 mm to 2 mm (page 39, line 26 teaches the mixing chamber height is 400um, i.e. 0.4 mm).
Regarding claim 51, modified Harvengt fails to teach wherein the mixing chamber comprises at least two of the baffles; and the at least one of the baffles is present on each side of the mixing chamber between the proximal end and distal end of the mixing chamber.
Fu teaches a microfluidic chemical analysis system device comprising a cross-flow-guiding micro static mixer (paragraph [0002]; Figs. 1-5). Fu teaches purpose of mixing is to reduce heterogeneity, for example for dilution, or to enhance the rate of chemical reactions, so it is very important to achieve fast and efficient mixing (paragraph [0004]). Fu teaches the device comprises a mixing chamber (Figs. 1-3, elements 6 and 7) and the mixing chamber includes at least two baffles present on each side of the mixing chamber between two ends of the mixing chamber (Figs. 1-3, guide blocks 4, 4’, 5, 5’). Fu teaches the invention has the following beneficial effects: by arranging alternating guide blocks in the pipeline, shear flow and extension flow can be generated in the flow field, the interface area between different fluids is increased, the molecular diffusion effect is enhanced, and ultimately uniform mixing at the molecular level is achieved (paragraph [0013]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the mixing chamber of modified Harvengt to incorporate the teachings of microfluidic devices comprising a mixing chamber with baffles of Fu (Figs. 1-3; paragraph [0013]) to provide: wherein the mixing chamber comprises at least two of the baffles; and the at least one of the baffles is present on each side of the mixing chamber between the proximal end and distal end of the mixing chamber. Doing so would have a reasonable expectation of successfully improving mixing as taught by Fu (paragraph [0013]).
Regarding claim 52, modified Harvengt fails to teach wherein the mixing chamber comprises comprising 4 to 100 of the baffles.
Fu teaches a microfluidic chemical analysis system device comprising a cross-flow-guiding micro static mixer (paragraph [0002]; Figs. 1-5). Fu teaches purpose of mixing is to reduce heterogeneity, for example for dilution, or to enhance the rate of chemical reactions, so it is very important to achieve fast and efficient mixing (paragraph [0004]). Fu teaches the device comprises a mixing chamber (Figs. 1-3, elements 6 and 7) and the mixing chamber includes at least two baffles present on each side of the mixing chamber between two ends of the mixing chamber (Figs. 1-3, guide blocks 4, 4’, 5, 5’). Fu teaches the invention has the following beneficial effects: by arranging alternating guide blocks in the pipeline, shear flow and extension flow can be generated in the flow field, the interface area between different fluids is increased, the molecular diffusion effect is enhanced, and ultimately uniform mixing at the molecular level is achieved (paragraph [0013]). Fu teaches at least 4 baffles (Figs. 1-3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the mixing chamber of modified Harvengt to incorporate the teachings of microfluidic devices comprising a mixing chamber with at least 4 baffles of Fu (Figs. 1-3; paragraph [0013]) to provide: wherein the mixing chamber comprises comprising 4 to 100 of the baffles. Doing so would have a reasonable expectation of successfully improving mixing as taught by Fu (paragraph [0013]).
Claim 53 is rejected under 35 U.S.C. 103 as being unpatentable over Harvengt in view of Fu as applied to claim 37 above, and further in view of He et al. (CN105771765A; see machine translation).
Regarding claim 53, modified Harvengt fails to teach: wherein each baffle is 0.1 mm to 1 mm wide.
He teaches a microfluidic system comprising a micro-mixer (paragraph [0002]; Fig. 3), wherein micromixers are known to include passive micromixers that mainly use microchannels with complex geometric structures (such as adding baffles and opening grooves in microchannels) to form chaotic convection to increase the convection intensity of the fluid, thereby increasing the contact area of fluid mixing and improving the mixing efficiency (paragraph [0005]). He teaches a microfluidic system (Figs. 3-4) comprising a mixing chamber (3) with baffles (5). He teaches a channel width of 0.1-0.2mm (paragraph [0023) and the width L4 of the baffle is equal to the width of the channel, i.e. 0.1-0.2mm (paragraph [0025]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified each baffle of modified Harvengt to incorporate the teachings of microfluidic systems with baffles having a width of 0.1-0.2mm of He (paragraphs [0023],[0025]) to provide wherein each baffle is 0.1 mm to 1 mm wide. Doing so would have a reasonable expectation of successfully providing for improved mixing efficiency as discussed by He (paragraph [0005]).
Additionally, since He teaches a width of a baffle of 0.1-0.2mm (paragraphs [0023],[0025]), which overlaps the claimed range of 0.1-1mm, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified each baffle of modified Harvengt to incorporate the teachings of baffles having a width of 0.1-0.2mm of He (paragraphs [0023],[0025]) to provide: wherein each baffle is 0.1 mm to 1 mm wide. I.e., it would have been prima facia obvious to have selected the overlapping portion of the ranges from the taught range of He (paragraphs [0023],[0025]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Claim 54 is rejected under 35 U.S.C. 103 as being unpatentable over Harvengt in view of Fu as applied to claim 37 above, and further in view of Chen et al. (Chen et al., “Numerical and experimental investigation on micromixers with serpentine microchannels”, International Journal of Heat and Mass Transfer 98 (2016) 131–140) and Norikane et al. (EP 1810746 A1; cited in the IDS filed 11/04/2022).
Regarding claim 54, Harvengt further teaches wherein:
(i) the mixing chamber: (A) has 25 mm in length (page 9, line 9 and page 32, line 25 teach the length of the mixing chamber is 2.5 cm), (B) has a rectangular cross-section perpendicular to the length (page 9, lines 10-11), and (C) comprises a first side, a second side, a top wall, a bottom wall (page 9, lines 10-16 teaches the mixing chamber has rectangular cross-section, therefore has first and second sides and top and bottom walls), wherein:
the top wall and bottom wall are: parallel to each other, run the length of the mixing chamber (Fig. 1 and page 9, lines 10-16 teaches the mixing chamber has rectangular cross-section, therefore the top and bottom walls are parallel and run the length of the chamber) and spaced to provide the mixing chamber with a depth (Fig. 1 and page 9, lines 10-16 teaches the mixing chamber has rectangular cross-section, which has a depth);
the first side and second side are: parallel to each other, run the length of the mixing chamber (Fig. 1 and page 9, lines 10-16 teaches the mixing chamber has rectangular cross-section, therefore the first and second sides are parallel and run the length of the chamber);
(ii) the one first inlet channel: (A) is located about centrally at the proximal end of the mixing chamber (Fig. 1; page 32, lines 26-27), (B) has a rectangular cross-section (page 8, lines 15-16 and 29-31);
(iii) the two second inlet channels: (A) are identical in shape (page 8, lines 26-28), (B) are located at each of the parallel sides along the length on the proximal end of the mixing chamber (Fig. 1 and page 8, third paragraph and lines 32-35, teaches two inlets located at parallel sides along the length of the mixing chamber for delivery of a second solution; page 9, fourth paragraph), (C) each have rectangular cross-section (8, lines 15-16 and 29-31); and
each of the directions of flow from the one first inlet channels and the two second inlet channels into the mixing chamber are substantially parallel to the general direction of flow in the mixing chamber (page 8, lines 32-35).
Modified Harvengt fails to teach:
the mixing chamber comprising 12 of the baffles;
the top wall and the bottom wall are spaced to provide the mixing chamber with a depth of 0.5 mm; the first side and second side are spaced 1.6 mm apart;
six of the 12 baffles are located on the first side, six of the 12 baffles are located on the second side, the first baffle is located on the first side 4.4 mm from the proximal end of the mixing chamber, the second baffle is located on the second side 6.132 mm from the proximal end of the mixing chamber, each baffle on the first side is separated from the next baffle on the first side by 3.464 mm, each baffle on the second side is separated from the next baffle on the second side by 3.464 mm, each baffle is trapezium in shape and has a length of from 0.25 mm to 0.55 mm and a width of 0.5 mm;
(ii) the one first inlet channel: (C) has a width of 0.27 mm, (E) and has a depth of 0.5 mm;
(iii) the two second inlet channels (D) each have a width of 0.1 mm, and (E) each have a depth of 0.5 mm.
Harvengt teaches the mixing chamber having a cross-sectional area of 0.2-3.2 mm2 (e.g. 0.6-1.0 mm2), a long side, i.e. spacing between sides, of 1.4-3.2 mm (e.g. 1.6-2.4 mm), a short side, i.e. depth, of 0.1-1.2 mm (e.g. 0.32-0.48 mm) (page 9, lines 10-12).
Since Harvengt teaches a depth of 0.1-1.2mm and spacing between sides of 1.4-3.2mm (page 9, lines 10-12), which overlaps the claimed range of a depth of 0.5 mm and the first side and second side are spaced 1.6 mm apart, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the dimensions of the mixing chamber of modified Harvengt to incorporate the teachings of dimension ranges of the mixing chamber of Harvengt (page 9, lines 10-12) to provide: the top wall and the bottom wall are spaced to provide the mixing chamber with a depth of 0.5 mm; the first side and second side are spaced 1.6 mm apart. I.e., it would have been prima facia obvious to have selected the overlapping portion of the ranges from the taught range Harvengt (page 9, lines 10-12) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Modified Harvengt fails to teach:
the mixing chamber comprising 12 of the baffles;
six of the 12 baffles are located on the first side, six of the 12 baffles are located on the second side, the first baffle is located on the first side 4.4 mm from the proximal end of the mixing chamber, the second baffle is located on the second side 6.132 mm from the proximal end of the mixing chamber, each baffle on the first side is separated from the next baffle on the first side by 3.464 mm, each baffle on the second side is separated from the next baffle on the second side by 3.464 mm, each baffle is trapezium in shape and has a length of from 0.25 mm to 0.55 mm and a width of 0.5 mm;
(ii) the one first inlet channel: (C) has a width of 0.27 mm, (E) and has a depth of 0.5 mm;
(iii) the two second inlet channels: (D) each have a width of 0.1 mm, and (E) each have a depth of 0.5 mm.
Harvengt teaches optimal operating conditions will depend on the precise configuration of the device and the desired characteristics of the product (page 15, lines 6-7). Harvengt teaches suitable ratio of flow rates between the first and second solutions (page 15, lines 8-24). Harvengt teaches the cross-sectional area of inlets is 0.02-0.32 mm2, such as 0.04-0.16 mm2 (page 8, lines 20-22). Harvengt teaches an inlet with a width of 0.2 mm and depth of 0.4 mm (page 8, lines 29-31).
MPEP 2144.05 (II)(B) holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of microfluidic devices, the selection of optimal experimental conditions including structural geometry and dimensions affects fluidic transport parameters such as pressure and flow rate which in turn affect mixing characteristics of desired fluids in a mixing chamber (Harvengt, page 8, lines 29-31, discusses ranges of ratios of flow rates between the first and second solutions, which relate to the first and second inlet channels). Thus, the width and depths of the first and second inlet channels are a result effective variables.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the one first inlet channel and the two second inlet channels of modified Harvengt to incorporate the teachings of ranges of cross-sectional areas of inlets, suitable ratios of flow rates between the first and second solutions, and optimizing configuration of the device of Harvengt (page 8, lines 20-22; page 15, lines 6-24) to provide: (ii) the one first inlet channel: (C) has a width of 0.27 mm, (E) and has a depth of 0.5 mm; (iii) the two second inlet channels: (D) each have a width of 0.1 mm, and (E) each have a depth of 0.5 mm through routine experimentation (MPEP 2144.05 (II)). I.e., it would have been obvious to design and fabricate the inlet channels to modify the result-effective variables, i.e. width and depth, and arrive at the claimed dimensions through routine optimization of workable dimensions for microfluidic channels to optimize the flow rates for each inlet and the ratio of flow rates between the first and second inlet channels.
Modified Harvengt fails to teach:
the mixing chamber comprising 12 of the baffles;
six of the 12 baffles are located on the first side, six of the 12 baffles are located on the second side, the first baffle is located on the first side 4.4 mm from the proximal end of the mixing chamber, the second baffle is located on the second side 6.132 mm from the proximal end of the mixing chamber, each baffle on the first side is separated from the next baffle on the first side by 3.464 mm, each baffle on the second side is separated from the next baffle on the second side by 3.464 mm, each baffle is trapezium in shape and has a length of from 0.25 mm to 0.55 mm and a width of 0.5 mm.
Fu teaches a microfluidic chemical analysis system device comprising a cross-flow-guiding micro static mixer (paragraph [0002]; Figs. 1-5). Fu teaches purpose of mixing is to reduce heterogeneity, for example for dilution, or to enhance the rate of chemical reactions, so it is very important to achieve fast and efficient mixing (paragraph [0004]). Fu teaches the device comprises a mixing chamber (Figs. 1-3, elements 6 and 7) and the mixing chamber includes baffles (Figs. 1-3, guide blocks 4, 4’, 5, 5’). Fu teaches the mixing chamber comprising at least 12 baffles (Figs. 1-3), 6 of the at least 12 baffles are located on a first side and 6 of the 12 baffles are located on a second side of the mixing chamber (Figs. 1-3). Fu teaches the invention has the following beneficial effects: by arranging alternating guide blocks in the pipeline, shear flow and extension flow can be generated in the flow field, the interface area between different fluids is increased, the molecular diffusion effect is enhanced, and ultimately uniform mixing at the molecular level is achieved (paragraph [0013]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the mixing chamber of Harvengt to incorporate the teachings of microfluidic devices comprising a mixing chamber with baffles of Fu (Figs. 1-3; paragraph [0013]) to provide: the mixing chamber comprising 12 of the baffles; six of the 12 baffles are located on the first side, six of the 12 baffles are located on the second side. Doing so would have a reasonable expectation of successfully improving mixing as taught by Fu (paragraph [0013]).
Modified Harvengt fails to teach:
the first baffle is located on the first side 4.4 mm from the proximal end of the mixing chamber, the second baffle is located on the second side 6.132 mm from the proximal end of the mixing chamber, each baffle on the first side is separated from the next baffle on the first side by 3.464 mm, each baffle on the second side is separated from the next baffle on the second side by 3.464 mm, each baffle is trapezium in shape and has a length of from 0.25 mm to 0.55 mm and a width of 0.5 mm.
Chen teaches analysis of micromixers with serpentine microchannels (abstract). Chen structural designs of microchannels affect mixing performances (abstract). Chen teaches different types of wall protrusions on microfluidic mixings are known and geometric parameters have an effect on mixing performances (page 132, left column, first paragraph). Chen teaches a microfluidic device (Fig. 4a) where the structural design area for micromixers are located 4.7 mm from an end of a mixing channel (Fig. 1a).
Since Chen teaches a distance of 4.7 mm between an end and a micromixer structure (Fig. 4a) that is merely close to the claimed dimension of 4.4 mm, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first baffle modified Harvengt to provide: the first baffle is located on the first side 4.4 mm from the proximal end of the mixing chamber. See MPEP 2144.05 (I). I.e., a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close (Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)).
Modified Harvengt fails to teach:
the second baffle is located on the second side 6.132 mm from the proximal end of the mixing chamber, each baffle on the first side is separated from the next baffle on the first side by 3.464 mm, each baffle on the second side is separated from the next baffle on the second side by 3.464 mm, each baffle is trapezium in shape and has a length of from 0.25 mm to 0.55 mm and a width of 0.5 mm.
Harvengt teaches the mixing chamber should be of adequate length to allow for mixing to be substantially complete by the time liquid reaches the outlet (page 9, line 7-8). Harvengt teaches the mixing chamber has a length of 1-10 cm in length, especially 1.5-5cm (page 9, lines 8-9).
Chen teaches analysis of micromixers with serpentine microchannels (abstract). Chen structural designs of microchannels affect mixing performances (abstract). Chen teaches different types of wall protrusions on microfluidic mixings are known and geometric parameters have an effect on mixing performances (page 132, left column, first paragraph). Chen teaches experimentation of various shapes and sizes of structural areas of structures of a micromixer (section 3.2), which includes distances between structures, lengths of structures, and widths of structures (Fig. 4).
MPEP 2144.05 (II)(B) holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of microfluidic devices, specifically mixing structures, the selection of optimal experimental conditions including structural geometry and dimensions affects fluidic transport parameters which in turn affect mixing performances of desired fluids in a mixing chamber (Chen, page 132, left column, first paragraph). Thus, the location of the baffles, separation distances between the baffles, and length and width of the baffles are a result effective variables.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the one first inlet channel and the two second inlet channels of modified Harvengt to incorporate the teachings of ranges of the length of the mixing chamber of Harvengt (page 9, lines 8-9) and the teachings of experimentation of various structural designs of micromixers of Chen (page 132, left column, first paragraph; section 3.2; Fig. 4) to provide: the second baffle is located on the second side 6.132 mm from the proximal end of the mixing chamber, each baffle on the first side is separated from the next baffle on the first side by 3.464 mm, each baffle on the second side is separated from the next baffle on the second side by 3.464 mm, each baffle has a length of from 0.25 mm to 0.55 mm and a width of 0.5 mm through routine experimentation (MPEP 2144.05 (II)). I.e., it would have been obvious to design and fabricate the baffles to have modified the result-effective variables, i.e. the location of the baffles, separation distances between the baffles, and length and width of the baffles, to arrive at the claimed invention through routine optimization of workable dimensions for baffles within microchannels to optimize the mixing performance within the mixing chamber to ensure adequate mixing of the solutions.
While Chen teaches different types of wall protrusions on microfluidic mixings are known and geometric parameters have an effect on mixing performances (page 132, left column, first paragraph), and shapes include rectangular, circular, and triangular structures (Fig. 4), modified Harvengt fails to teach: each baffle is trapezium in shape.
Norikane teaches a method using a microfluidic device (Figs. 1-2) comprising the inlets (10, 11), baffles (14), and a mixing chamber (12), comprising the following steps: (a) mixing in the device a first solution and a second solution comprising water (paragraph [0008] teaches merging plural types of fluid that are incompatible with each other; paragraph [0099] teaches surfactant is mixed with water). Norikane teaches the baffles (Fig. 1) are trapezium in shape (Fig. 1; paragraph [0018]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified each baffle of modified Harvengt to incorporate the teachings of mixing structures being different shapes of Chen (Fig. 4) and trapezium baffles of Norikane (Fig. 1) to provide: each baffle is trapezium in shape. Doing so would have a reasonable expectation of successfully allowing for mixing of fluids within the chamber. Additionally, doing so would have been a mere change in shape of each baffle, where the trapezium shape would have been an obvious matter of choice in view of Chen and Norikane (MPEP 2144.04 (IV)(B); In reDailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966)).
In an alternative interpretation of claim 37, claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over Harvengt et al. (WO 2018219521 A1; cited in the IDS filed 08/27/2024) in view of Fu et al. (CN 1542429 A; see machine translation). For compact prosecution purposes, in this alternative interpretation, the claim limitation of “0.8mm to 0.12 mm wide” is interpreted as “0.08 mm to 0.12 mm wide”.
Regarding claim 37, Harvengt teaches a method of manufacturing a liposomal adjuvant using a microfluidic device (page 5, lines 35-36; Fig. 1),
the microfluidic mixing device (Fig. 1; pages 7-10) comprising:
(i) a mixing chamber (Fig. 1; page 7, “mixing chamber”);
(ii) one first inlet channel (Fig. 1 and page 8, second paragraph, teaches at least one inlet for delivery of a first solution; page 9, fourth paragraph), which is into the mixing chamber (page 8, second paragraph);
(iii) two second inlet channels (Fig. 1 and page 8, third paragraph, teaches two inlets for delivery of a second solution; page 9, fourth paragraph), which are into the mixing chamber (page 8, third paragraph);
(iv) an outlet (Fig. 1 and page 8, last paragraph; page 9, fourth paragraph), which is from the mixing chamber (Fig. 1 and page 8, last paragraph);
wherein:
the one first inlet channel and two second inlet channels are disposed substantially symmetrically at a proximal end of the mixing chamber (Fig. 1 and page 9, fourth paragraph) and the outlet is at a distal end of the mixing chamber (Fig. 1 and page 9, fourth paragraph);
the method comprising:
(a) mixing in the device mixing chamber a first solution and a second solution, thereby obtaining a mixed material comprising the liposomal adjuvant (page 6, lines 1-2, teaches mixing in the device a first solution comprising a solvent, phosphatidylcholine lipid and a sterol, and a second solution comprising water and the saponin, therefore comprises a mixed material comprising a liposomal adjuvant; page 15 teaches mixing of the first and second solutions in the mixing chamber; page 16 teaches upon mixing of the first and second solutions, liposomes will form), the first solution being delivered into the mixing chamber by the one first inlet channel (page 8, second paragraph; page 9, fourth paragraph) and comprising a solvent and a lipid (page 6, lines 1-2, “solvent, phosphatidylcholine lipid and a sterol”), the second solution comprising water (page 6, lines 1-2) and being delivered into the mixing chamber by the two second inlet channels (page 8, third paragraph; page 9, fourth paragraph), the mixed material exiting the mixing chamber by the outlet (page 8, last paragraph teaches an outlet for recover of the mixed material, therefore mixed materials exits the mixing chamber by the outlet); and
(b) removing the solvent from the mixed material (page 6, line 3).
While Harvengt teaches the desire to facilitate adequate mixing (page 8, lines 13-14), Harvengt fails to teach: the mixing chamber comprising a baffle; and the two second inlet channels are each from 0.08 mm to 0.12 mm wide.
Harvengt teaches optimal operating conditions will depend on the precise configuration of the device and the desired characteristics of the product (page 15, lines 6-7). Harvengt teaches suitable ratio of flow rates between the first and second solutions (page 15, lines 8-24). Harvengt teaches the cross-sectional area of inlets is 0.02-0.32 mm2, such as 0.04-0.16 mm2 (page 8, lines 20-22). Harvengt teaches inlets are 0.16-0.24 mm wide (page 9, lines 15-16). Harvengt teaches an inlet with a width of 0.2 mm and depth of 0.4 mm (page 8, lines 29-31).
MPEP 2144.05 (II)(B) holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of microfluidic devices, the selection of optimal experimental conditions including structural geometry and dimensions (i.e. width) affects fluidic transport parameters such as pressure and flow rate which in turn affect mixing characteristics of desired fluids in a mixing chamber (Harvengt, page 8, lines 29-31, discusses ranges of ratios of flow rates between the first and second solutions, which relate to the first and second inlet channels). Thus, the width of the second inlet channels are a result effective variables.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the two second inlet channels of Harvengt to incorporate the teachings of ranges of cross-sectional areas of inlets, suitable ratios of flow rates between the first and second solutions, and optimizing configuration of the device of Harvengt (page 8, lines 20-22; page 15, lines 6-24) to provide: the two second inlet channels are each from 0.08 mm to 0.12 mm wide through routine experimentation (MPEP 2144.05 (II)). I.e., it would have been obvious to design and fabricate the second inlet channels to modify the result-effective variables, i.e. width, and arrive at the claimed dimensions through routine optimization of workable dimensions for microfluidic channels to optimize the flow rates for each inlet and the ratio of flow rates between the first and second inlet channels.
Additionally, since Harvengt teaches widths of inlet channels (page 9, lines 15-16, 0.16-0.24 mm wide; page 8, lines 29-31, 0.2 mm wide) that are merely close to the claimed dimensions of 0.08-0.12 mm, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the two second inlet channels of Harvengt to provide: the two second inlet channels are each from 0.08 mm to 0.12 mm wide. See MPEP 2144.05 (I). I.e., a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close (Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)).
Modified Harvengt fails to teach: the mixing chamber comprising a baffle.
Fu teaches a microfluidic chemical analysis system device comprising a cross-flow-guiding micro static mixer (paragraph [0002]; Figs. 1-5). Fu teaches purpose of mixing is to reduce heterogeneity, for example for dilution, or to enhance the rate of chemical reactions, so it is very important to achieve fast and efficient mixing (paragraph [0004]). Fu teaches the device comprises a mixing chamber (Figs. 1-3, elements 6 and 7) and the mixing chamber includes baffles (Figs. 1-3, guide blocks 4, 4’, 5, 5’). Fu teaches the invention has the following beneficial effects: by arranging alternating guide blocks in the pipeline, shear flow and extension flow can be generated in the flow field, the interface area between different fluids is increased, the molecular diffusion effect is enhanced, and ultimately uniform mixing at the molecular level is achieved (paragraph [0013]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the mixing chamber of modified Harvengt to incorporate the teachings of microfluidic devices comprising a mixing chamber with baffles of Fu (Figs. 1-3; paragraph [0013]) to provide: the mixing chamber comprising a baffle. Doing so would have a reasonable expectation of successfully improving mixing as taught by Fu (paragraph [0013]).
Response to Arguments
Applicant’s arguments, see pages 9-10, filed 03/30/2026, with respect to the drawing and claim objections have been fully considered and are persuasive. The drawing and claim objections of 10/24/2025 have been withdrawn.
Applicant's arguments, see pages 10-16, filed 03/30/2026, with respect to the rejections under 35 U.S.C. 103, specifically regarding amended claim 37, have been fully considered but they are not persuasive.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning (Remarks, page 13), it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d `7, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Additionally, applicant provides a conclusory argument against the rejection of each and every claim (Remarks, page 13), which does not elaborate on why it is not obvious to combine the references to arrive at the claimed limitations.
Focusing on the independent claim 37, as discussed above in the rejection of claim 37 under 35 U.S.C. 103, while Harvengt teaches the desire to facilitate adequate mixing (page 8, lines 13-14), Harvengt fails to teach: the mixing chamber comprising a baffle.
Fu provides teachings of a microfluidic chemical analysis system (Figs. 1-5, paragraph [0002]), which is in the same field of art as Harvengt. Fu provides teachings of microfluidic devices comprising a mixing chamber with baffles of Fu (Figs. 1-3; paragraph [0013]). Fu also provides motivation that the invention has the following beneficial effects: by arranging alternating guide blocks in the pipeline, shear flow and extension flow can be generated in the flow field, the interface area between different fluids is increased, the molecular diffusion effect is enhanced, and ultimately uniform mixing at the molecular level is achieved (paragraph [0013]).
Therefore, it would have been obvious to one of ordinary skill in the art to have modified the mixing chamber of Harvengt to incorporate the teachings of microfluidic devices comprising a mixing chamber with baffles of Fu (Figs. 1-3; paragraph [0013]) to provide: the mixing chamber comprising a baffle. Doing so would have a reasonable expectation of successfully improving mixing as taught by Fu (paragraph [0013]).
Thus, there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art to have arrived at the claimed invention in view of the prior art.
In response to applicant’s argument that the prior art fails to teach “two second inlet channels…are each from 0.8 mm to 0.12 mm wide” (Remarks, page 13), the examiner disagrees. Harvengt teaches: two second inlet channels (Fig. 1 and page 8, third paragraph, teaches two inlets for delivery of a second solution; page 9, fourth paragraph), which are into the mixing chamber (page 8, third paragraph) and are each from 0.8 mm to 0.12 mm wide (page 32, lines 27-28, teaches the inlets are 0.2 mm wide, which is within the range of 0.8 mm to 0.12 mm, i.e. 0.12mm-0.80mm).
In response to applicant’s argument of the rejection of claim 37 of unexpected or surprising effect (Remarks, page 13, last paragraph – page 14, first paragraph), specifically that “FIG. 6 shows that, "Surprisingly, mixing performance appeared to be mainly driven by the width of the external channels; mixing chamber width seemed to have less impact on the mixing." (See from page 69, line 21, to page 70, line 4, of the specification.)…When "two second inlet channels, which...are each from 0.8 mm to 0.12 mm wide" as in "CapExt" (see page 69, lines 3-5), the alfa values "[s]urprisingly" increase (see page 70, lines 3 and 4)”, the examiner disagrees. Note that applicant’s arguments are regarding the limitation of “two second inlet channels, which...are each from 0.8 mm to 0.12 mm wide” of claim 37.
First, applicant presents arguments regarding unexpected effects or results and MPEP 716.02 states that evidence of unexpected results may be sufficient to overcome an obviousness rejection. However, the limitation being argued of “two second inlet channels, which…are each from 0.8 mm to 0.12 mm wide”, is taught by the primary reference of Harvengt. Harvengt teaches two second inlet channels (Fig. 1 and page 8, third paragraph, teaches two inlets for delivery of a second solution; page 9, fourth paragraph), which are into the mixing chamber (page 8, third paragraph) and are each from 0.8 mm to 0.12 mm wide (page 32, lines 27-28, teaches the inlets are 0.2 mm wide, which is within the range of 0.8 mm to 0.12 mm, i.e. 0.12mm-0.80mm). The obviousness rejection of claim 37 combines Fu with primary reference Harvengt to arrive at the claimed “the mixing chamber comprising a baffle”, which is not argued by applicant’s arguments of surprising effects.
Second, if applicant is arguing against obviousness of the limitation of “two second inlet channels, which...are each from 0.8 mm to 0.12 mm wide” of claim 37, applicant’s argument regarding unexpected results or effects must be established by factual evidence (MPEP 716.01(c)(I)) and arguments presented by the applicant cannot take the place of evidence in the record (MPEP 716.01(c)(II)). While Applicant discusses Fig. 6 and page 63, lines 3-5, and pages 69, line 21 – page 70, line 4 of the instant application (Remarks, page 13, last paragraph – page 14, first paragraph), the applicant has not presented sufficient evidence, such as any experimental data comparing applicant’s claimed second inlet channels with experimental data of the closest prior art. Therefore, applicant’s assertions of unexpected results constitute mere argument.
Third, applicant’s arguments and evidence regarding unexpected effects or results, such as Fig. 6 showing alfa values for specific channel dimensions (Remarks, page 13, last paragraph – page 14, first paragraph) is not commensurate in scope with the claimed invention. Claim 37 recites “two second inlet channels, which...are each from 0.8 mm to 0.12 mm wide”. However, Claim 37 does not recite the specific dimensions of the mixing chamber and first inlet channel as shown in Fig. 6 of the instant application which provide the surprising mixing performance. Additionally, “mixing performance” and the “alfa values” are not claimed. Furthermore, the instant specification, page 69, line 21 – page 70, line 4 discloses that the “best mixing performance, was obtained using a microfluidic device having a mixing chamber width of 1 mm, external channel width of 0.1 mm and internal channel width of 0.2 mm.” Since claim 37 only recites dimensions of the two second inlet channels “are each from 0.8 mm to 0.12 mm wide”, the evidence is not commensurate in scope with the claimed invention, which has a range broader and different from the originally disclosed range.
Thus, the arguments and evidence of surprising effects or unexpected results are not sufficient to overcome the rejection of claim 37 under 35 U.S.C. 103. Applicant’s arguments regarding unexpected effects (Remarks, page 13, last paragraph – page 14, first paragraph) are unpersuasive and fail to demonstrate unexpected result by the preponderance of the evidence.
In response to applicant’s argument, see pages 14-16, with respect to the rejections that relied on MPEP 2144.05(I), the examiner disagrees. Additionally, note that it is unclear which specifically claim applicant is arguing against in pages 14-16. Examiner is interpreting the argument as relating to the rejection of claim 54 under 35 U.S.C. 103.
MPEP 2144.05(I) states a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close (Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
Since Chen teaches a distance of 4.7 mm between an end and a micromixer structure (Fig. 4a) that is merely close to the claimed dimension of 4.4 mm, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first baffle modified Harvengt to provide: the first baffle is located on the first side 4.4 mm from the proximal end of the mixing chamber. See MPEP 2144.05 (I). I.e., a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close (Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)). While applicant refers to In re Patel , note that the rejection does not refer or rely on the precedent of In re Patel, but rather the precedent of at least Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) as discussed in MPEP 2144.05(I).
Additionally, MPEP 2144.05 (II)(B) holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of microfluidic devices, specifically mixing structures or baffles, the selection of optimal experimental conditions including structural geometry and dimensions affects fluidic transport parameters which in turn affect mixing performances of desired fluids in a mixing chamber (Chen, page 132, left column, first paragraph). Thus, the location of the baffles, separation distances between the baffles, and length and width of the baffles are a result effective variables.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first baffle of modified Harvengt to incorporate the teachings of baffle at a distance of 4.7 mm between an end and a micromixer structure of Chen (Fig. 4a) that is merely close to the claimed dimension of 4.4 mm and the teachings of experimentation of various structural designs of micromixers of Chen (page 132, left column, first paragraph; section 3.2; Fig. 4) to provide: the first baffle is located on the first side 4.4 mm from the proximal end of the mixing chamber through routine experimentation (MPEP 2144.05 (II)). I.e., it would have been obvious to design and fabricate the baffles to have modified the result-effective variables, i.e. the location of the baffles, to arrive at the claimed invention through routine optimization of workable location and distances for baffles within microchannels to optimize the mixing performance within the mixing chamber to ensure adequate mixing of the solutions.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mueth et al. (US 11243494 B2; effectively filed 04/15/2016; cited in the IDS filed 08/27/2024) teaches an apparatus for separating blood and trapping (abstract). Mueth teaches channels that are 110 microns wide, i.e. 0.11mm (column 37, lines 47-49).
O’Connor et al. (US 20020097633 A1; cited in the IDS filed 08/27/2024) teaches a microfluidic mixing devices with multiple fluid streams (abstract). O’Connor teaches channels can have a width of 10-10000 microns, i.e. 0.01-10mm (paragraph [0084]).
Gaitan et al. (US 20100202928 A1; cited in the IDS filed 08/27/2024) teaches an apparatus including microchannels (abstract; Fig. 1). Gaitan teaches channels have a width ranging from 10-100 microns, i.e. 0.01-0.10 mm (paragraph [0032]).
Hood et al. (US 20150115488 A1; cited in the IDS filed 08/27/2024) teaches microfluidic systems (abstract). Hood teaches buffer counter flow channels were 1.2mm wide (paragraph [0093]).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HENRY H NGUYEN whose telephone number is (571)272-2338. The examiner can normally be reached M-F 7:30A-5:00P.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
Prosecution Insights