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 .
Claim Objections
The previous objection to claim 8 has been withdrawn.
Specification
The previous objection to the specification has been withdrawn. The substitute specification has been accepted.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Response to Arguments
Applicant’s arguments and amendments, filed 3/4/2026, with respect to the rejection(s) of claim(s) 1, 2, 15, 16, 28, 29, 32 and 39 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Butler et al. (US 2018/0207639 A1), have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Pattky et al. ("Advantages and limitations of a new cationic coating inducing a slow electroosmotic flow for CE-MS peptide analysis: a comparative study with commercial coatings." Anal. Bioanal. Chem. (2013) 405: 225 - 237. Published online: 17 October 2012; hereinafter “Pattky”).
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 (i.e., changing from AIA to pre-AIA ) 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.
Claim(s) 1, 2, 8, 15, 16, 28, 29 and 32 – 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Butler et al. (US 2018/0207639 A1; hereinafter “Butler”) in view of Pattky et al. (Martin Pattky and Carolin Huhn, "Advantages and limitations of a new cationic coating inducing a slow electroosmotic flow for CE-MS peptide analysis: a comparative study with commercial coatings." Anal. Bioanal. Chem. (2013) 405: 225 - 237. Published online: 17 October 2012; hereinafter “Pattky”).
Regarding claim 1, Butler teaches a microfluidic system (microfluidic trap 1000; paragraph 53; figure 1) for isolating or detecting nucleic acids, comprising:
a microcapillary (microcapillary 1050; paragraphs 4, 53 and 56) having a first end and a second end with a length (L) longer than a width (W),
and wherein one or more inner surfaces of the microcapillary are coated with a coating (the microcapillary can be coated with a neutral compound or neutral polymer; paragraphs 4 and 54);
a fluid inlet (inlet area 1010 and entry region 1020) at the first end fluidically connected to the microcapillary;
a fluid outlet (outlet area 1030 and exit region 1040) at the second end fluidically connected to the microcapillary, and
a buffer (DNA buffer solutions; paragraph 86).
PNG
media_image1.png
499
838
media_image1.png
Greyscale
Butler does not specifically teach wherein one or more inner surfaces of the microcapillary are coated with a coating that is polycationic and wherein the coating enhances electroosmotic flow.
The microcapillary inner surface structure comprises inner surfaces of the microcapillary 1050, the microcapillary inlet 1060 and the microcapillary outlet 1070 (paragraph 53; figure 1).
Butler does teach that the electroosmotic flow can allow particles to escape the microfluidic trap 1000 because the electroosmotic flow generated can be larger than the velocity of the electrophoretic flow (paragraph 54).
Pattky teaches a polycationic capillary coating comprising poly(diallyldimethylammonium) chloride that provides a relatively high EOF (electroosmotic flow) (see Abstract and page 226, left column, last paragraph).
It would have been logical to consider coating the microcapillary inlet 1060 surface and the microcapillary outlet 1070 surface with a polycationic coating that enhances electroosmotic flow in order to facilitate the introduction and withdraw, respectively, of sample fluids containing the nucleic acids. Enabling the enhancement or increase in electroosmotic flow would facilitate the effective withdraw of the sample fluid from the electrophoretic flow from the device. The rationale to support an obviousness rejection under 35 U.S.C. 103 may rely on logic and sound scientific principle (see MPEP § 2144.02). The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success (see MPEP § 2143.02). Furthermore, the use of a polycationic coating material such as poly(diallyldimethylammonium) chloride with the recognized property of providing a relatively high or enhanced electroosmotic flow is well known in the art as recognized by Pattky. Therefore, the selection of poly(diallyldimethylammonium) chloride as a polycationic capillary surface coating for the inlet and outlet inner surfaces of the microcapillary would have been considered to be suitable and predictable to a person of ordinary skill in the art. The selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art (see MPEP § 2144.07). The Supreme Court stated in KSR that "when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.'" The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). In addition, the simple substitution of one known element for another is likely to be obvious when predictable results are achieved (see MPEP § 2143, B.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide wherein one or more inner surfaces of the microcapillary are coated with a coating that is polycationic and wherein the coating enhances electroosmotic flow. Examiner submits that these arguments are in line with the Supreme Court unanimous opinion, KSR International v. Teleflex, Inc., 127 S. Ct. 1727, 1741 (2007), in which the Court stated that “[a] court must ask whether the improvement is more than the predictable use of prior art elements according to their established functions.” Id. at 1731.
Regarding claim 2, Butler teaches the microfluidic device system of claim 1, wherein the first end, the second end, or both are greater in cross-sectional area than the section of microcapillary between the first and second ends (paragraphs 56 – 59; figure 1).
Regarding claim 8, Pattky teaches wherein the coating is poly(diallyldimethylammonium) chloride (PDADMAC) (page 226, left column, last paragraph).
Regarding claim 15, Butler teaches the system of claim 1, further comprising an electric current generator configured to generate an electrophoretic flow through the microcapillary (paragraphs 6, 55, 68, 81 and 87).
Regarding claim 16, Butler teaches the system of claim 1, further comprising an inlet tank fluidically connected to the fluid inlet and an outlet tank fluidically connected to the fluid outlet (e.g., a tank or container; paragraphs 41 and 42).
Regarding claim 28, Butler teaches a method for isolating or detecting nucleic acids (paragraphs 7, 38 – 40 and 70), comprising providing the system of claim 1;
providing a sample comprising nucleic acids to the sample inlet or sample injection port of the microcapillary (paragraph 41);
generating a fluid flow from the fluid inlet to the fluid outlet with a centerline velocity v. along a longitudinal axis of the microcapillary (paragraphs 62 and 68); and
providing an electric current to the microcapillary, wherein the electric current is configured to generate an electrophoretic velocity ve that is directionally opposed to the fluid flow and centerline velocity vo (electrophoretic flow is generated in the microfluidic trap 1000 comprising the microcapillary 1050 in opposition to a fluid flow; paragraphs 52, 53, 55 and 81; figure 1); and
detecting or isolating nucleic acids at a stagnation region of interest near the fluid inlet (paragraphs 7, 56, 62, 63, 66, 67 and 70).
Regarding claim 29, Butler teaches the method of claim 28, further comprising illuminating the microfluidic device system with light from a light source for a period of time prior to providing the sample (e.g., for visual observation the exit region was illuminated using a light source and imaged; paragraphs 20, 63, 83, 89, 91, 92; figure 12).
Regarding claim 32, Butler teaches the method of claim 28, wherein a ratio of centerline velocity vo to electrophoretic velocity ve about 20 to about 200 (see figure 7).
Regarding claim 33, Butler does not specifically teach the method of claim 32, wherein the centerline velocity vo is about 4 mm/s to about 12 mm/s.
However, Butler does teach that the flow velocities can be varied to effect optimal sample separation and concentration (e.g., paragraph 104). Therefore, the centerline flow velocity can be considered to be a known-result-effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide the specified centerline flow velocities as claimed.
Regarding claim 34, Butler does not specifically teach the method of claim 32, wherein the electrophoretic velocity ve is about -0.03 mm/s to about -0.15 mm/s or about +0.03 mm/s to about +0.15 mm/s.
However, Butler does teach that the electrophoretic flow can be varied to effect optimal sample separation and concentration (e.g., paragraphs 54, 55 and 104; figures 7 and 21; claims 1 and 16). Therefore, the centerline flow velocity can be considered to be a known-result-effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide the specified electrophoretic flow velocities as claimed.
Regarding claims 35 – 38, Butler does not specifically teach the recited nucleic acids, but does teach that the disclosed apparatus and methods can be applied to nucleic acid samples in general and known samples (e.g., paragraphs 3, 7 and 38 – 40). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide the method for the recited nucleic acids as claimed.
Regarding claim 39, Butler teaches the method of claim 28, wherein detecting or isolating nucleic acids at the stagnation region of interest near the fluid inlet (the apparatus and method can allow the user to tune the stagnation region or point where the particle of interest is concentrated and/or trapped; paragraphs 56, 60 and 63) comprises isolating DNA and RNA and detecting only RNA or only DNA (paragraphs 3, 7 and 38 – 40).
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Butler and Pattky, and further in view of Su et al. (US 2005/0250117 A1; hereinafter “Su”).
Regarding claim 9, modified Butler does not specifically teach the microfluidic device system of claim 1, wherein the microfluidic device system comprises one or more of polymethylmethacrylate (PMMA), polydimethylsiloxane (PDMS), polycarbonate, polystyrene, polyethylene, or glass.
However, Su teaches similar microfluidic systems comprising PMMA, PDMS and glass (paragraph 55). The selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art (see MPEP § 2144.07). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide wherein the microfluidic device system comprises one or more of polymethylmethacrylate (PMMA), polydimethylsiloxane (PDMS), or glass.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Butler and Pattky, and further in view of Staats (US 2002/0100714 A1; hereinafter “Staats”).
Regarding claim 11, modified Butler does not specifically teach the microfluidic devices system of claim 1, further comprising a sample injection port fluidically connected to the microcapillary and positioned in between the fluid inlet and fluid outlet on the first end of the microcapillary.
However, Staats teaches a relevant microfluidic apparatus comprising a microfluidic capillary channel with a sample injection port 13 positioned at positions along the microfluidic channel (figures 4 and 5; paragraphs 51 and 55). As shown by Staats, the sample injection port can be incorporated into the microfluidic device depending on design choice and wherein microfluidic channel access is desired. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide wherein a sample injection port fluidically connected to the microcapillary and positioned in between the fluid inlet and fluid outlet on the first end of the microcapillary.
Claim(s) 18 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Butler and Pattky, and further in view of Kopf-Sill et al. (US 6,858,185 B1; hereinafter “Kopf-Sill”).
Regarding claim 18, modified Butler does not specifically teach the system of claim 1, further comprising a syringe pump in fluidic communication with the fluid outlet.
Regarding claim 21, modified Butler does not specifically teach the system of claim 1, further comprising a pump to drive fluid motion through the system.
Butler does teach the use of pressure driven flow with the system (paragraphs 48 and 66).
However, the use of syringe pumps with microfluidic apparatus is well known in the art as evidenced by Kopf-Sill for facilitating fluid flow within the apparatus (col. 32, 1 – 10). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide a syringe pump in fluidic communication with the fluid outlet and to drive fluid motion through the system.
Claim(s) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Butler and Pattky, and further in view of Crooks et al. (US 2005/0034990 A1; hereinafter “Crooks”).
Regarding claim 25, modified Butler does not specifically teach the system of claim 1, further comprising a micrograph image collecting apparatus.
Butler does teach the use of an apparatus for obtaining representative microscopic fluorescence images (figures 6A – 6D; paragraph 14).
However, Crooks teaches a relevant microfluidic apparatus incorporating an imaging device 214 for obtaining micrograph images of analytes within the system 200 (paragraph 37). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide a micrograph image collecting apparatus with the system for collecting images.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN J. SINES whose telephone number is (571)272-1263. The examiner can normally be reached 9 AM-5 PM EST M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Elizabeth A Robinson can be reached at (571) 272-7129. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
BRIAN J. SINES
Primary Patent Examiner
Art Unit 1796
/BRIAN J. SINES/Primary Examiner, Art Unit 1796