DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 15, 2026 has been entered.
Preliminary Remark
Claims 1-21 are canceled.
Information Disclosure Statement
The IDS received on April 15, 2026 is proper and is being considered by the Examiner.
Claim Objections
Claim 40 is objected to because of the following informalities: claim recites the phrase, “analyzing images from generated from (b) …” It would appear the phrase should recite, “analyzing images generated from (b) …” instead. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The rejection of claims 22-42 under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as based on a disclosure which is not enabling, made in the Office Action mailed on March 2, 2026 is withdrawn in view of the Amendment received on April 15, 2026.
Double Patenting
The rejection of claims 22-44 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,265,088; claims 1-17 over of U.S. Patent No. 11,447,817; claims 1-20 over U.S. Patent No. 11,242,558; claims 1-13 over U.S. Patent No. 11,162,136; claims 1-16 of U.S. Patent No. 12,000,842, made in the Office Action mailed on March 2, 2026 is withdrawn in view of the Terminal Disclaimer filed with the Amendment received on April 15, 2026.
Rejection – Maintained
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
The rejection of claims 22-44 on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,542,546 (herein, “the ‘546 patent) in view of Jiang et al. (Eur. J. Clin. Microbiol. Infect. Dis., January 2016, pages 415-422), made in the Office Action mailed on March 2, 2026 is maintained for the reasons of record.
The Amendment received on April 15, 2026 does not have a terminal disclaimer over the ‘546 patent in the Amendment received on April 15, 2026.
Rejection – New Grounds, Necessitated by IDS
Claims 22-44 are also rejected under the same ground of non-statutory double-patenting rejection over claims 1-21 of 19/063,118 (herein, “the ‘118 application) in view of Jiang et al. (Eur. J. Clin. Microbiol. Infect. Dis., January 2016, pages 415-422), for the same reasons as discussed below over the ‘546 patent.
The Office notes that the ‘118 application has since issued as a patent and therefore, a terminal disclaimer is required.
Claims 22-44 also rejected under the same ground of non-statutory double-patenting rejection over claims 14-23 of 19/400,892 (herein, “the ‘892 application) in view of Jiang et al. (Eur. J. Clin. Microbiol. Infect. Dis., January 2016, pages 415-422), for the same reasons as discussed below over the ‘546 patent.
The Rejection:
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The rejection rationale is analogous to that of the rejection over the ‘546 patent in view of Jiang et al. as discussed below based on an obvious application of a digital assay of the conflicting patents.
In order the reduce the redundancies of rejections, only the rejection over the ‘546 patent over Jiang et al. is detailed below.
With regard to instant claim 1, claims of the ‘546 patent also claims a method comprising, performing a digital analysis of a sample distributed across a set of partitions (see claim 1), wherein the performing the digital analysis comprise imaging a set of cross-sections of a closed container containing the set of partitions (“wherein performing the digital analysis comprises imaging a set of cross-sections of a closed container containing the set of partitions … and wherein the digital analysis is performed within three minutes”, see claim 1).
With regard to instant claim 25, the set of partitions comprises a set of droplets of an emulsion generated using the sample (“set of partitions comprises a set of droplets of an emulsion generated from the sample”, see claim 5) wherein the clarity of the emulsion is produced without refractive index matching of the sample and other materials of the solution (“wherein clarity of the emulsion is produced without refractive index matching of the sample and other materials of the emulsion”, see claim 5).
With regard to instant claim 27, each droplet of the set of droplets has a diameter from 31 microns to 100 microns (see claim 6, “each of the set of droplets has a … diameter from 10 microns to 100 microns”).
With regard to instant claim 29, the performing of the digital analysis comprises scanning the set of cross-sections of the closed container comprising the readout of fluorescent signals from individual partitions represented in each of the set of cross-sections (see claim 31).
With regard to instant claim 30, the scanning is performed using known forms of detection (“performing a 3D scanning technique”, claim 14; “planar imaging”, claim 15).
With regard to instant claim 31, the closed container has a volume from 31 to 100 microliters (“the closed container has a volume from 10 to 100 microliters”, see claim 8).
With regard to instant claim 33, the ‘546 patent also claims that the method is digital analysis of a set of aqueous droplets generated from a sample and retained within a continuous aqueous layer2 within a closed container (see claim 16), and that the set of droplets has a number greater than 500,000 droplets (see claim 21, wherein 3.5 million droplets are claimed).
With regard to instant claims 37, 38, and 41, claims of the ‘546 patent claims a method employing sample from cell-free nucleic acids (see claim 11), or fetal or maternal cell (claim 12). In addition, application of digital amplification to detect presence of disease markers such as cancer would have been an obvious application of a technology known in the art to be applied for molecular diagnostics.
With regard to instant claim 39, the aqueous droplet is characterized by sample occupancy of less than 5% (see claim 7).
With regard to instant claim 40, the droplets are great in number so as to not require the Poisson Distribution correction (see claim 9). Because the invention of the ‘546 patent achieves the feature based on the capability of increasing the number of droplets present in the closed container, with limits as great as “greater than 3.5 million droplets” (see claim 21), any number higher would have been an obvious application of the method of the ‘546 patent.
The claims of the ‘546 patent do not explicitly claim the many different types of samples that the “digital” counting/quantification of a sample that can be employed.
Consequently, the ‘546 patent do not claim that the method can be applied for detecting the antimicrobial susceptibility (claim 22, in-part, claim 34), utilizing a fluorescent growth inhibitor, live-dead staining component (claims 23, 24, 28, and 35), or that the droplets (or partitions) contain one to zero bacterial sample (claims 26 and 36) or returning the results of the assay within less than one day (claim 32).
Jiang et al. teach a well-known means of detecting antimicrobial susceptibility testing using droplet-based detection (“[w]e present the MilliDrop Analyzer (MDA), a droplet-based millifluidic system for digital antimicrobial susceptibility testing (D-AST)”, Abstract).
Jiang et al. the steps of distributing the sample comprising bacteria and antibiotic (“[l]iquid medium … antibiotic solution, and bacterial suspensions are converged at the first junction into an aqueous stream, which meets the carrier fluid (HFE oil, Novec, France) and the spacing fluid (mineral oil, Sigma-Aldrich, France) at the second junction. HFE oil, as an immiscible phase, is injected at a constant flow rate to break up the aqueous stream (bacteria and antibiotic mixture) and the spacing fluid into alternating AST droplets … Each AST droplet functions a an individual reactor with spacing droplets … In each test, an aqueous stream with constant bacterial density of 1.5 x 106 CFU/mL and alternating antibiotic concentration … was injected to generate an AST droplet”, page 416, bottom paragraph to page 417, 1st column).
The artisans teach detection from the droplets containing the bacteria and antibiotic agent:
“1 mM of red fluorescent sulforhodamine 101 … was premixed with the antibiotic solution … 87 mM of resazurin … was premixed with the bacterial suspension to act as a metabolic reporter of bacterial growth in the droplets … Blue and non-fluorescent resazurin is irreversible reduced into pink and highly fluorescent resorufin by viable bacteria [live-dead stain]” (page 417, 2nd column)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the claimed method of the ‘546 patent for assays conventionally applied in the art of digital detection of target analytes such as the teachings of Jiang et al., thereby arriving at the invention as claimed for the following reasons.
The art if digital analysis method has been well-established before the effective filing date of the claimed invention. The premise of the digital analysis, such as digital amplification (PCR) is in the mass distribution of sample into a plurality of droplets so as to achieve, on average, zero to one copy of the target analyte per droplet, wherein the detection or absence of the signals per droplet is correlate to the presence/absence and quantity of the analyte present in the sample. In order to achieve the quantification, Poisson Distribution correction is performed.
The invention of the ‘546 patent is directed to the ability to image the plurality of droplets in a closed compartment, wherein the number of the droplets is in great quantity, so as to achieve one or zero number of target analyte per droplet, that the Poisson Distribution correction is unnecessary, and in the ability to account for signals generated from each droplet within the closed container.
Therefore, one of ordinary skill in the art would have recognized that the method of detection of the ‘546 patent would have been applicable to detect target analytes or assays that involve digital analysis, such as the method pertaining to bacterial susceptibility as taught by Jiang et al., for the motivation of not needing to rely on Poisson Distribution correction typically required in a digital quantitation method, yielding the predictable outcome of the ‘546 patented method.
As to providing the result of the assay result within less than one day, Jiang et al. explicitly teach that their digital bacterial susceptibility assay is produced in less than 2 hours when testing fast-growing strains such as E. coli (“[i]n the MDA, reliable MIC results can be obtained in less than 2 h when we test fast-growing strains such as E. coli”, page 420, 2nd column). Therefore, providing the results of the assay in a timely manner within less than a day would have not only been possible, but obvious in view of art’s desired in obtaining reliable and fast test result.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized 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.” Id.
Therefore, the invention as claimed is prima facie obvious over the claims of the ‘546 patent in view of Jiang et al.
Conclusion
No claims are allowed.
Claims are free of prior art. The prior art does not teach or suggest a method of performing a digital analysis of analytes that are distributed in a plurality (set) of partitions within a closed container, wherein the analysis involves imaging a set of cross-sections of the container containing the plurality of partitions.
Digital analysis analytes require the distribution of droplets containing the analytes that allows for the imaging of the droplets (or partitions) using a conventional scanner, but does not require the imaging multiple cross sections of the container containing the droplets (or partitions), nor is there a reason to do so.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 July 1, 2026
/YJK/
1 Instant claim 29 was held indefinite, but best possible interpretation is assumed for the purpose of prosecution.
2 The Office assumes that this continuous layer is “fluid” as the claim was rejected under 112, 1st new matter.
Prosecution Insights