DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 17 NOVEMBER 2025 has been entered.
Status of Claims
The claim set submitted the RCE on 17 NOVEMBER 2025 is acknowledged and considered. In the claim set, Claims 1 and 22 are ‘Currently Amended’; Claims 2-7, 9-16, 19-21, 23-34 and 37-39 are ‘Original’ or ‘Previously Presented’.
Current pending claims are Claims 1-7, 9-16, 19-22, 23-34 and 37-39 and are considered on the merits below.
Response to Amendment/Arguments
In the instant claims, Claims 1 and 22 have been amended to recite how the thermoplastic prepolymer has been cured by exposure to UV-light when included as part of the microfluidic device claim. The language of “that has been partially cured by exposure to UV-light” is directed to product by process language. The language directed to how the molded and partially cured thermoplastic is made does not structurally distinguish it or provide distinct structural characteristics.
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) See also: United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1373, 2023 USPQ2d 862 (Fed. Cir. 2023) and Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016).
If the structure is implied by the process, then the process steps would be considered when assessing the patentability of the product-by-process claims.
In the REMARKS, Applicant recited on pages 10-13, showing how the device is made which does not distinguish it from the prior art. Specially on page 12, these steps are directed how the device is manufactured and Applicant does not distinguish it from how it is structurally different from the applied references. The exposure to UV light does not structurally differentiate or distinguish it from any other thermoplastic that is used in a microfluidic device. Applicant’s invention is directed to a device. The process steps newly added do not structurally distinguish it from the prior art. The product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979) .
“The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature” than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an nonobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983).
Applicant has not provided any evidence to show of the method step of how a prepolymer that has been partially cured by exposure to UV-light would physically or structurally distinguish it from the applied references.
On page 13, Applicant asserts that the applied references do no teach the configured to language of claim 1. However, the Examiner has mapped in this rejection below and in previous rejection how the reference are the same structurally. Features of an apparatus may be recited either structurally or functionally. In re Schreiber, 128 F.3d 1473, 1478, 44 USPQ2d 1429, 1432 (Fed. Cir. 1997). The configured to language is directed to functional language of the device, and the Examiner has concluded that the functional limitation is an inherent characteristic of the prior art and therefore satisfies the configured to language. The burden then shifts to applicant to establish that the prior art does not possess the characteristic relied on. In re Schreiber, 128 F.3d at 1478, 44 USPQ2d at 1432; In re Swinehart, 439 F.2d 210, 213, 169 USPQ 226, 228 (CCPA 1971) . “Where the Patent Office has reason to believe that a functional limitation asserted to be critical for establishing novelty in the claimed subject matter may, in fact, be an inherent characteristic of the prior art, it possesses the authority to require the applicant to prove that the subject matter shown to be in the prior art does not possess the characteristic relied on.” Furthermore, “[A]pparatus claims cover what a device is, not what a device does.” Hewlett-Packard Co.v.Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a “recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus” if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987) .
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, 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 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Applicant asserts that “None of the cited references, either alone or in any combination thereof, teach or suggest a microfluidic device or use thereof wherein the device comprises "a first molded thermoplastic prepolymer that has been partially cured by exposure to UV-light". As discussed above, the newly added portion of the claims in both Claim 1 and Claim 22 do not further define the device structurally as they are directed to product by process language and Applicant has not provided any evidence to show of the method step of how a prepolymer that has been partially cured by exposure to UV-light would physically or structurally distinguish it from the applied references.
Furthermore, Applicant asserts that “There remains no motivation to combine these references. Church requires extended dwell time to allow lysis by the electric field, which would be contrary to the faster speeds employed by Wurm. Lu also utilizes electric field for electroporation and is concerned with dwell times, but additionally specifically designed the device to allow a narrower distance between electrode tips without causing mechanical disruption of the cells.” In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-7, 9-16, 19-34 and 37-39 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the mold" in the first wherein clause. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites “between the first and second thermoplastic prepolymers”; is the “between the first and second thermoplastic prepolymers” supposed to be referring to the “first molded and partially cured thermoplastic prepolymer” and the “second, partially cured thermoplastic prepolymer”? It is unclear if the thermoplastics that is newly added is the same or different than the molded and partially cured thermoplastic prepolymer.
Dependent Claims 2-7, 9-16 and 19-21 are also rejected under 112(b) and being dependent upon a rejected claim.
Claim 22 recites the limitation "the mold" in the newly added portion in the first wherein clause. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites “between the first and second thermoplastic prepolymers”; is the “between the first and second thermoplastic prepolymers” supposed to be referring to the “first molded and partially cured thermoplastic prepolymer” and the “second, partially cured thermoplastic prepolymer”? It is unclear if the thermoplastics that is newly added is the same or different than the molded and partially cured thermoplastic prepolymer.
Dependent Claims 23-34 and 37-39 are also rejected under 112(b) and being dependent upon a rejected claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1, 2, 4-7, 10, 12-16, 19, 22, 23, 25-28 and 30-34 are rejected under 35 U.S.C. 103 as being unpatentable over CHURCH, Integrated electrical concentration and lysis of cells in a microfluidic chip, Biomicrofluidics, 2010, 4, 044101, submitted on the Information Disclosure Statement on 09 JANUARY 2019; Non-Patent Literature Documents Cite No. 3, in view of LU, A microfluidic electroporation device for cell lysis, Lab Chip, 2005, 5, 23–29, in view of WURM, Lab Chip,2012,12,1071, in view of CARLBORG, HARALDSSON, Lab Chip, 2011, 11, 3136, herein referred ‘HARALDSSON’.
Applicant’s invention is drawn towards a device, a microfluidic device.
Regarding Claim 1, the reference CHURCH discloses a microfluidic device for lysing cells, title, abstract, the microfluidic device, page 044101-2, microfluidic chip, comprising: a molded polymer, page 044101-2; one or more microfluidic channels, Figure 1, page 044101-2, each channel comprising constricted regions and non- constricted regions separating the constricted regions, Figure 1, page 044101-2, wherein the constricted regions are configured to disrupt the cellular membranes of cells in fluid flowing through the one or more microfluidic channels, abstract, page 044101-3.
The CHURCH reference discloses the claimed invention, but silent in regards to more than one constricted regions, and non-constricted regions in series, such that the non-constricted regions are between the constricted regions, the constriction regions have a width of 2-10 mm such that the constricted regions are configured to disrupt the cellular membranes of 85-100 % of cells in fluid flowing through the one or more microfluidic channels and wherein the non-constricted regions being shaped to converge at the ends into the constricted regions.
The LU reference discloses a continuous flow microfluidic device for lysing cells, Figure 3 and 6, abstract, page 25, Section 3.2.1, the microfluidic device comprising: a first molded and partially cured prepolymer, page 24, Section 2.2, Figure 1; a second layer, page 24, Section 2.2, Figure 1; wherein the first molded and partially cured prepolymer is removed from the mold and is contacted to the second layer, page 24, Section 2.2, Figure 1, wherein the first molded and partially cured prepolymer and the second layer are bonded together, page 24, Section 2.2, Figure 1, wherein the resulting microfluidic device is configured for continuous flow of fluidic samples, Figure 3 and 6, page 25, Section 3.2.1, and wherein the microfluidic device has therein: one or more microfluidic channels, Figure 3 and 7, each channel comprising more than one constricted regions, Figure 3 and 6, see annotated Figure 3 below, constricted regions is considered to be the areas of the SAW-tooth where the points are the closest indicated by dotted rectangle, and non-constricted regions in series, such that the non-constricted regions separating are between the constricted regions, Figure 3 and 6, see annotated Figure 3 below, non-constricted regions is considered to be the areas of the SAW-tooth where the points are the furthest indicated by solid ovals, the non-constricted regions being shaped to converge at the ends into the constricted regions, Figure 3, 6 and 7, see annotated Figure 3 below, wherein each of the constricted regions have a width in the range of mm such that the constricted regions, Figure 3, are configured to disrupt the cellular membranes of the cells in fluid flowing through the one or more microfluidic channels, abstract, page 27 and 28, Table 1, page 26, Section 3.3.
Annotated Figure 3 of LU.
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It would be obvious to one having ordinary skill in the art before the effective filing date to modify the CHURCH reference wherein the non-constricted regions being shaped to converge at the ends into the constricted regions and where the non-constricted regions are in series, such that the non-constricted regions are between the constricted regions as taught by LU to increase possibility of cell lysis in the device and be able to have tunable operating condition for speed and selectivity of lysis, as well as potential for integration with upstream and downstream microfluidic components, page 23, Introduction, page 25, Section 3.2.1.
The LU discloses the first molded prepolymer as mapped above, but does not disclose the prepolymer that has been partially cured by exposure to UV-light.
The language directed to how the molded and partially cured thermoplastic is made does not structurally distinguish it or provide distinct structural characteristics.
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) See also: United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1373, 2023 USPQ2d 862 (Fed. Cir. 2023) and Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016).
The language of how the plastic is cured does not structurally distinguish it from the prior art. The product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979) .
The combination of CHURCH in view of LU suggests the claimed invention, but is silent in regards to the width of the constricted regions.
The WURM reference discloses a microfluidic device for lysing cells, abstract, lab-on-a-chip/microfluidic system, lysis of mammalian cells, the microfluidic device comprising: a substrate, Figure 1, page 1074, Section 2.3, comprising one or more microfluidic channels, Figure 1, white arrow ‘Fluid flow’, or any other black space between nozzles, each channel comprising more than one constricted regions, Figure 1, page 1072, medium gray labeled with ‘Cell compression in 3 mm wide gap’, or Figure 1 narrowed space between nozzles, and non-constricted regions separating the constricted regions, Figure 1, before and after locations of the ‘Cell compression’ area, the non- constricted regions being shaped to converge at the ends into the constricted regions, Figure 1 and 2, wherein each of the constricted regions have a width of 2.5-10 mm, 3mm gap, Section 3.2, such that the constricted regions are configured to disrupt the cellular membranes of 85-100% of cells in fluid flowing through the one or more microfluidic channels, Figure 5, page 1075.
Below is the characterization of Figure 1 as it applies to the instant claim language.
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The disclosure of WURM uses the term ‘nozzle’ and ‘micronozzles’ interchangeably, see Figure 1, Section 2.3. In the rejection below the terms ‘nozzle’ and ‘micronozzles’ are referring to the same thing and are interchangeable.
WURM teaches that not only is the size of the gap important in lysing cells, but also the cell diameter and the flow rate through the constriction. It can be seen in Figure 5, at a 3 mm gap at least 85-100 % at 40 mL min-1, cells are disrupted, Section 3.1.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the CHURCH in view of LU references with the constricted regions to have a width between 2.5-10 mm, so that a cell of a critical diameter is able to lysed, WURM Section 3.2, 3.3, Figure 4 and 5.
The combination above suggests the claimed invention, but is silent in regards to wherein the microfluidic device comprising: a first molded and partially cured thermoplastic prepolymer that has been partially cured by exposure to UV-light, bonded to a second, partially cured thermoplastic prepolymer that has been partially cured by exposure to UV-light.
The HARALDSSON discloses a microfluidic device, Figure 4, comprising: a first molded and partially cured thermoplastic prepolymer, bonded to a second, partially cured thermoplastic prepolymer, Figure 4, page 3141-3142, Moulding process and Bonding process.
As mentioned above, the language directed to how the molded and partially cured thermoplastic is made does not structurally distinguish it or provide distinct structural characteristics.
In addition, the language direct to how the thermoplastics prepolymers are bonded not structurally distinguish it or provide distinct structural characteristics. The only structural characteristic in the section of the claim language that has patentable weight is that a there are a first and second thermoplastic prepolymer that makes up the microfluidic device. How the prepolymers are made has no patentable weight.
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) See also: United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1373, 2023 USPQ2d 862 (Fed. Cir. 2023) and Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016).
The language of how the plastic is cured does not structurally distinguish it from the prior art. The product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979) .
It would be obvious to one having ordinary skill in the art before the effective filing date to have the microfluidic device comprising: a first molded and partially cured thermoplastic prepolymer, bonded to a second, partially cured thermoplastic prepolymer as taught by HARALDSSON so that the device can maintain its shape/form without cracking, page 3140, and remain a device with low gas permeability, page 3140.
Additional Disclosures Included by the combination are: Claim 2: wherein the device of claim 1, wherein the two or more microfluidic channels are parallel to each other, CHURCH Figure 1, LU, Figure 3 and 7, page 044101-2, WURM, Figure 1.; Claim 6: wherein the device of claim 1, wherein there are 1-40 microfluidic channels, CHURCH Figure 1, page 044101-2, LU, Figure 3 and 7, WURM Figure 2, array of nozzles.; Claim 7: wherein the device of claim 1, wherein each microfluidic channel comprises 3- 15 constricted regions, LU, Figure 3, 6 and 7.; Claim 10: wherein the device of claim 1, wherein each microfluidic channel comprises 10 constricted regions, LU, Figure 3, 6 and 7; Claim 12: wherein the device of claim 1, wherein each of the each constricted region has a width of 2.5-4.5mm, WURM Figure 1, 3mm gap, Section 3.2.; Claim 13: wherein the device of claim 1, is suggested by the combination including wherein each of the microfluidic channels has 4 constricted regions, LU, Figure 3, 6 and 7 and WURM further discloses in Figure 2, two consecutive nozzle arrays were manufactured, page 1074, Figure 2, where each constricted region has a width of 3 mm. WURM further teaches that consecutive nozzle orientation is sufficient for a complete cell disruption, page 1074, Section 3.1. It would be obvious to one having ordinary skill in the art before the effective filing date to have each microfluidic channel comprises 4 constricted regions to have a higher percentage of lysed cells in the sample, Section 3.1, and to have tunable operating conditions for speed and selectivity of the lysis, LU, page 23, Introduction.; Claim 14: wherein the device of claim 1, wherein there are 20 microfluidic channels, LU, Figure 7, WURM Figure 2, there are at least 20 micronozzles in the array.; Claim 15; wherein the device of claim 1, wherein there are 40 microfluidic channels, LU, Figure 7, WURM, Figure 2 there are at least 40 micronozzles in the array.; Claim 16: wherein the device of claim 1, wherein the microfluidic channels are configured to support a flow rate from about 20 mL/min to about 2000 mL/min, LU, page 23, Introduction, page 28, optimal lysis can be achieved by fine tuning flow rate of cell suspension, selectivity of speed of lysis, WURM, Figure 5, page 1075-1076, Section 3.3.; and Claim 19: wherein the device of claim 1, wherein the microfluidic device is configured to withstand high fluid pressure without deformation of the constricted regions, LU, page 23, Introduction, page 28, optimal lysis can be achieved by fine tuning flow rate of cell suspension , WURM, page 1074, Section 2.2.
Regarding Claim 4, the combination above discloses the claimed invention, but is silent in regards to wherein each of the non-constricted regions has a width of 40-100 m.
The CHURCH reference teaches the width of the non- constricted regions has a width of 400 m. The LU reference teaches the width of the non-constricted regions have a width of 130 mm, Figure 3.
In Figure 1 of WURM, there is a scale in the lower right corner of the darkened lower Figure. Based on the scale of Figure 1, the non-constricted region appears to have a width of 40 m.
It would have been obvious to one having ordinary skill in the art before the effective filing date to modify the width of the non-constricted region to be 40-100 m, to allow a flow of cells at a desired flow rate and since the CHURCH and LU references’ channel is subjected to SU-8 developer to create width, it would be obvious to modify the non-constricted region to be 40-100 m as a matter of design choice based on the size of the cell to be lysed. In addition it would be obvious to one having ordinary skill in the art to modify the width of the non-constricted regions has a width of 40-100 m in WURM to prevent any channel clogging before the constricted regions, abstract, page1074.
Regarding Claim 5, the combination above discloses the claimed invention, but is silent in regards wherein each of the non-constricted regions has a length of 60- 120 m, and each of the constricted regions has a length of 10-20 m.
The CHURH reference discloses the constricted region has a length of 200 m and the length of the entire channel is 1 cm. The length of the non-constricted region is 1 cm minus the length of the constricted region, page 004410-2, Figure 1. LU further teaches each of the non-constricted regions has a length of 60- 120 m, Figure 3, 90 mm.
The CHURCH reference teaches the width of the non- constricted regions has a width of 400 m, and each of the constricted regions has a width of 15 m.
It would have been obvious to one having ordinary skill in the art before the effective filing date to modify the length of the non-constricted region with a length of 60- 120 m, and each of the constricted regions has a length of 10-20 m to continuous operation and tunable operating conditions for speed and selectivity of the lysis, LU, Introduction, page 23.
Applicant’s invention is drawn towards a method.
Regarding Claim 22, the reference CHURCH discloses a method for continuous flow cell lysis in a microfluidic device, abstract, page 044101-3 to 044101-4, the method comprising: providing a microfluidic device for lysing cells, title, abstract, the microfluidic device, page 044101-2, microfluidic chip, comprising: one or more microfluidic channels, Figure 1, page 044101-2, each channel comprising constricted regions and non- constricted regions separating the constricted regions, Figure 1, page 044101-2, wherein the constricted regions are configured to disrupt the cellular membranes of cells in fluid flowing through the one or more microfluidic channels, abstract, page 044101-3; flowing fluid through the microfluidic device, page 044101-3 to 044101-4, whereby cells in the fluid are lysed, abstract, page 044101-3, wherein the microfluidic device comprises one or more microfluidic channels, page 044101-2, Figure 1, each channel comprising a constricted region and non-constricted regions separating the constricted regions, page 044101-2, Figure 1, wherein the constricted regions are configured to disrupt the cellular membranes of cells in fluid flowing through the one or more microfluidic channels, abstract, page 044101-3.
The CHURCH reference discloses the claimed invention, but silent in regards to more than one constricted regions, and non-constricted regions in series, such that the non-constricted regions are between the constricted regions, the constriction regions have a width of 2-10 mm such that the constricted regions are configured to disrupt the cellular membranes of 85-100 % of cells in fluid flowing through the one or more microfluidic channels and wherein the non-constricted regions being shaped to converge at the ends into the constricted regions.
The LU reference discloses a method for continuous flow cell lysis in a microfluidic device, page 23, Introduction, the method comprising: providing a microfluidic device, Figure 3, 6 and 7, wherein the continuous flow microfluidic device for lysing cells, Figure 3 and 6, abstract, page 25, Section 3.2.1, comprising: a first molded and partially cured prepolymer, page 24, Section 2.2, Figure 1; a second layer, page 24, Section 2.2, Figure 1; wherein the first molded and partially cured prepolymer is removed from the mold and is contacted to the second layer, page 24, Section 2.2, Figure 1, wherein the first molded and partially cured prepolymer and the second layer are bonded together, page 24, Section 2.2, Figure 1, wherein the resulting microfluidic device is configured for continuous flow of fluidic samples, Figure 3 and 6, page 25, Section 3.2.1, the microfluidic device comprising: wherein the microfluidic device has therein: one or more microfluidic channels, Figure 3 and 7, each channel comprising more than one constricted regions, Figure 3 and 6, see annotated Figure 3 below, constricted regions is considered to be the areas of the SAW-tooth where the points are the closest indicated by dotted rectangle, and non-constricted regions in series, such that the non-constricted regions separating are between the constricted regions, Figure 3 and 6, see annotated Figure 3 below, non-constricted regions is considered to be the areas of the SAW-tooth where the points are the furthest indicated by solid ovals, the non-constricted regions being shaped to converge at the ends into the constricted regions, Figure 3, 6 and 7, see annotated Figure 3 below, wherein each of the constricted regions have a width in the range of mm such that the constricted regions, Figure 3, are configured to disrupt the cellular membranes of the cells in fluid flowing through the one or more microfluidic channels, abstract, page 27 and 28, Table 1, page 26, Section 3.3, continuously flow fluid through the microfluidic device, page 23, Introduction, page 25, Section 3.2.1, page 25, Section 2.3, dispense cells by a syringe pump, lysing the cells in the fluid by passing cells through the constricted regions, page 25, Section 3.1 and 3.2, Figure 12, wherein the constricted regions are configured to disrupt the cellular membranes of the cells in fluid flowing through the one or more microfluidic channels, abstract, page 27 and 28, Table 1, page 26, Section 3.3, Figure 12.
Annotated Figure 3 of LU.
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It would be obvious to one having ordinary skill in the art before the effective filing date to modify the CHURCH reference wherein the non-constricted regions being shaped to converge at the ends into the constricted regions and where the non-constricted regions are in series, such that the non-constricted regions are between the constricted regions as taught by LU to increase possibility of cell lysis in the device and be able to have tunable operating condition for speed and selectivity of lysis, as well as potential for integration with upstream and downstream microfluidic components, page 23, Introduction, page 25, Section 3.2.1.
The LU discloses the first molded prepolymer as mapped above, but does not disclose the prepolymer that has been partially cured by exposure to UV-light.
The language directed to how the molded and partially cured thermoplastic is made does not structurally distinguish it or provide distinct structural characteristics.
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) See also: United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1373, 2023 USPQ2d 862 (Fed. Cir. 2023) and Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016).
The language of how the plastic is cured does not structurally distinguish it from the prior art. The product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979) .
The combination of CHURCH in view of LU suggests the claimed invention, but is silent in regards to the width of the constricted regions.
The WURM reference discloses a method for continuous flow cell lysis in a microfluidic device, abstract, the method comprising: providing a microfluidic device, abstract, lab-on-a-chip/microfluidic system, lysis of mammalian cells, the microfluidic device comprises one or more microfluidic channels, Figure 1, white arrow ‘Fluid flow’, each channel comprising more than one constricted regions, Figure 1, page 1072, medium gray labeled with ‘Cell compression in 3 mm wide gap’ and all of narrowed black spaces between nozzles, and non-constricted regions separating the constricted regions, Figure 1, before and after locations of the ‘Cell compression’ area and before and after nozzles, the non- constricted regions being shaped to converge at the ends into the constricted regions, Figure 1 and 2, wherein each of the constricted regions have a width of 2.5-10 mm, 3mm gap, Section 3.2, flowing the fluid through the microfluidic device, Figure 1, ‘Fluid flow’, and, lysing the cells in the fluid by passing the cells through the constricted regions, wherein the constricted regions are configured to disrupt the cellular membranes of 85-100% of cells in fluid flowing through the one or more microfluidic channels, Figure 5, page 1075.
Below is the characterization of Figure 1 as it applies to the instant claim language.
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The disclosure of WURM uses the term ‘nozzle’ and ‘micronozzles’ interchangeably, see Figure 1, Section 2.3. In the rejection below the terms ‘nozzle’ and ‘micronozzles’ are referring to the same thing and are interchangeable.
WURM teaches that not only is the size of the gap important in lysing cells, but also the cell diameter and the flow rate through the constriction. It can be seen in Figure 5, at a 3 mm gap at least 85-100 % at 40 mL min-1, cells are disrupted, Section 3.1.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the CHURCH reference with the constricted regions to have a width between 2.5-10 mm, so that a cell of a critical diameter is able to lysed, WURM Section 3.2, 3.3, Figure 4 and 5.
The combination above suggests the claimed invention, but is silent in regards to wherein the microfluidic device comprising: a first molded and partially cured thermoplastic prepolymer that has been partially cured by exposure to UV-light, bonded to a second, partially cured thermoplastic prepolymer that has been partially cured by exposure to UV-light.
The HARALDSSON discloses a microfluidic device, Figure 4, comprising: a first molded and partially cured thermoplastic prepolymer, bonded to a second, partially cured thermoplastic prepolymer, Figure 4, page 3141-3142, Moulding process and Bonding process.
As mentioned above, the language directed to how the molded and partially cured thermoplastic is made does not structurally distinguish it or provide distinct structural characteristics.
In addition, the language direct to how the thermoplastics prepolymers are bonded not structurally distinguish it or provide distinct structural characteristics. The only structural characteristic in the section of the claim language that has patentable weight is that a there are a first and second thermoplastic prepolymer that makes up the microfluidic device. How the prepolymers are made has no patentable weight.
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) See also: United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1373, 2023 USPQ2d 862 (Fed. Cir. 2023) and Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016).
The language of how the plastic is cured does not structurally distinguish it from the prior art. The product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979) .
Additional Disclosures Included by the combination are: Claim 23: wherein the device of claim 22, wherein the two or more microfluidic channels are parallel to each other, Figure 1, page 044101-2, LU Figure 3, 6 and 7, WURM see nozzles are parallel to each other Figure 1 and 2.; Claim 27: wherein the device of claim 1, wherein there are 1-40 microfluidic channels, Figure 1, page 044101-2, LU, Figure 3, 6 and 7, WURM, Figure 1 and 2, array of nozzles.; Claim 28: wherein the method of claim 22, is wherein each microfluidic channel comprises 3- 15 constricted regions, LU , Figure 3, 6 and 7.; Claim 30: wherein the method of claim 22, wherein each of the each constricted region has a width of 2.5-4.5 mm, WURM Figure 1, 3mm gap, Section 3.2.; Claim 31: wherein the method of claim 22, wherein each of the microfluidic channels has 4 constricted regions, LU Figure 3, 6 and 7 and WURM further discloses in Figure 2, two consecutive nozzle arrays were manufactured, page 1074, Figure 2, where each constricted region has a width of 3 mm. WURM further teaches that consecutive nozzle orientation is sufficient for a complete cell disruption, page 1074, Section 3.1. It would be obvious to one having ordinary skill in the art before the effective filing date to have each microfluidic channel comprises 4 constricted regions to have a higher percentage of lysed cells in the sample, Section 3.1, and 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).; Claim 32: wherein the method of claim 22, wherein there are 20 microfluidic channels, WURM Figure 1 and 2, there are at least 20 nozzles in the array, LU Figure 7.; Claim 33: wherein the method of claim 22, wherein there are 40 microfluidic channels, WURM, Figure 1 and 2, there are at least 40 nozzles in the array, LU Figure 7.; and Claim 34: wherein the method of claim 22, wherein the microfluidic channels are configured to support a flow rate from about 20 mL/min to about 2000 mL/min, LU, page 23, Introduction, WURM, Figure 5, page 1075-1076, Section 3.3.
Regarding Claim 25, the combination above discloses the claimed invention, but is silent in regards to wherein each of the non-constricted regions has a width of 40-100 m.
The CHURCH reference teaches the width of the non- constricted regions has a width of 400 m. The LU reference teaches the width of the non-constricted regions have a width of 130 mm, Figure 3.
In Figure 1 of WURM, there is a scale in the lower right corner of the darkened lower Figure. Based on the scale of Figure 1, the non-constricted region appears to have a width of 40 m.
It would have been obvious to one having ordinary skill in the art before the effective filing date to modify the width of the non-constricted region to be 40-100 m, to allow a flow of cells at a desired flow rate and since the CHURCH and LU references’ channel is subjected to SU-8 developer to create width, it would be obvious to modify the non-constricted region to be 40-100 m as a matter of design choice based on the size of the cell to be lysed. In addition it would be obvious to one having ordinary skill in the art to modify the width of the non-constricted regions has a width of 40-100 m in WURM to prevent any channel clogging before the constricted regions, abstract, page1074.
Regarding Claim 26, the combination above discloses the claimed invention, but is silent in regards wherein each of the non-constricted regions has a length of 60- 120 m, and each of the constricted regions has a length of 10-20 m.
The CHURH reference discloses the constricted region has a length of 200 m and the length of the entire channel is 1 cm. The length of the non-constricted region is 1 cm minus the length of the constricted region, page 004410-2, Figure 1. LU further teaches each of the non-constricted regions has a length of 60- 120 m, Figure 3, 90 mm.
The CHURCH reference teaches the width of the non- constricted regions has a width of 400 m, and each of the constricted regions has a width of 15 m.
It would have been obvious to one having ordinary skill in the art before the effective filing date to modify the length of the non-constricted region with a length of 60- 120 m, and each of the constricted regions has a length of 10-20 m to continuous operation and tunable operating conditions for speed and selectivity of the lysis, LU, Introduction, page 23.
Claims 3, 9, 11, 24 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over CHURCH, Integrated electrical concentration and lysis of cells in a microfluidic chip, Biomicrofluidics, 2010, 4, 044101, submitted on the Information Disclosure Statement on 09 JANUARY 2019; Non-Patent Literature Documents Cite No. 3, in view of LU, A microfluidic electroporation device for cell lysis, Lab Chip, 2005, 5, 23–29, in view of WURM, Lab Chip,2012,12,1071, in view of CARLBORG, HARALDSSON, Lab Chip, 2011, 11, 3136, herein referred ‘HARALDSSON’, and further in view of HONG, US Publication No. 2005/0053952 A1, submitted on the Information Disclosure Statement on 09 JANUARY 2019; Non-Patent Literature Documents Cite No. 8.
Regarding Claim 3, the combination above discloses the claimed invention, but is silent in regards to wherein the non-constricted regions are arranged in a honeycomb- like pattern.
The HONG reference discloses a microfluidic device, abstract, for lysing cells, abstract, the microfluidic device comprising: one or more microfluidic channels, Figure 16 and 17B, each channel comprising constricted regions and non-constricted regions separating the constricted regions, Figure 16 and 17B, [0191, 0194], wherein the non-constricted regions are arranged in a honeycomb-like pattern and where there are 10 constricted regions, Figure 16 and 17B, and have more than 20 or 40 microfluidic channels, [0194].
It would have been obvious to one having ordinary skill in the art before the effective filing date to modify the microfluidic channel so that the non-constricted regions are arranged in a honeycomb-like pattern and have more than 10 constricted regions and have more than 20 or 40 microfluidic channels to performing multiple lysing in parallel and simultaneously.
Regarding Claim 9, the combination above discloses the claimed invention, but is silent in regards to wherein each microfluidic channel comprises a first segment of constricted regions along a fluid flow path having a width of 6-8 m and a second segment of constricted regions along a fluid flow path having a width of 4-6 m.
The HONG reference discloses a plurality of microfluidic channels, Figure 16 and 17B, 32A-D, [0190-0191], which comprises a first segment of constricted regions along a flow path of a first width and a second segment of constricted regions along a flow path of a second width, Figure 16, 32A -32D, each constricted regions are of different widths based on applications of utilizing the channels, [0109], and control the actuation of fluid occurring in the narrow portions, [0161].
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the microfluidic channel such that a first segment of constricted regions along a fluid flow path having a width of 6-8 m and a second segment of constricted regions along a fluid flow path having a width of 4-6 m based on the application of the flow channel, [0109], and to control the actuation and pressure of fluid through the channel, [0161], ], for cell disruption based on cell diameter.
Regarding Claim 11, the combination above discloses the claimed invention, but is silent in regards to wherein for each channel, the first five constricted regions along a fluid flow path have a width of 6.5 m, and the last five constricted regions along the fluid flow path have a width of 5 m.
The HONG reference discloses a plurality of microfluidic channels, Figure 16 and 17B, 32A-D, [0190-0191], which comprises a first segment of constricted regions along a flow path of a first width and a second segment of constricted regions along a flow path of a second width, Figure 16, 32A -32D, each constricted regions are of different widths based on applications of utilizing the channels, [0109], and control the actuation of fluid occurring in the narrow portions, [0161].
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the microfluidic channel such that the first five constricted regions along a fluid flow path have a width of 6.5 m, and the last five constricted regions along the fluid flow path have a width of 5 m, based on the application of the flow channel, [0109], and to control the actuation and pressure of fluid through the channel, [0161], for cell disruption based on cell diameter.
Regarding Claim 24, the combination above discloses the claimed invention, but is silent in regards to wherein the non-constricted regions are arranged in a honeycomb- like pattern.
The HONG reference discloses a microfluidic device, abstract, for lysing cells, abstract, the microfluidic device comprising: one or more microfluidic channels, Figure 16 and 17B, each channel comprising constricted regions and non-constricted regions separating the constricted regions, Figure 16 and 17B, [0191, 0194], wherein the non-constricted regions are arranged in a honeycomb-like pattern and where there are 10 constricted regions, Figure 16 and 17B, and have more than 20 or 40 microfluidic channels, [0194].
It would have been obvious to one having ordinary skill in the art before the effective filing date to modify the microfluidic channel so that the non-constricted regions are arranged in a honeycomb-like pattern and have more than 10 constricted regions and have more than 20 or 40 microfluidic channels to performing multiple lysing in parallel and simultaneously.
Regarding Claim 29, the combination above discloses the claimed invention, but is silent in regards to wherein each microfluidic channel comprises a first segment of constricted regions along a fluid flow path having a width of 6-8 m and a second segment of constricted regions along a fluid flow path having a width of 4-6 m.
The HONG reference discloses a plurality of microfluidic channels, Figure 16 and 17B, 32A-D, [0190-0191], which comprises a first segment of constricted regions along a flow path of a first width and a second segment of constricted regions along a flow path of a second width, Figure 16, 32A -32D, each constricted regions are of different widths based on application