DETAILED ACTION
The present Office Action is responsive to the Amendment received on November 25, 2025.
Preliminary Remark
Claims 1-21 are canceled.
Claims 42-44 are new.
Information Disclosure Statement
The IDS received on November 25, 2025 is proper and is being considered by the Examiner.
Claim Rejections - 35 USC § 112
The rejection of claims 25, 26, 29, and 36 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point out and distinctly claim the subject matter, made in the Office Action mailed on September 16, 2025 is withdrawn in view of the Amendment received on November 25, 2025.
The new matter rejection of claims 27, 31, and 33-41 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as failing to comply with the written description requirement made in the Office Action mailed on September 16, 2025 is withdrawn in view of the claim amendment and arguments presented in the Amendment received on November 25, 2025.
Rejection – Maintained & New Grounds, Necessitated by Amendment
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.
The rejection of claims 22-41 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 September 16, 2025 is maintained for the reasons of record. Applicants’ arguments presented in the Amendment received on November 25, 2025 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
In addition, claim 42 is rejected herein as being necessitated by Amendment (its addition).
The Rejection:
The disclosure does not enable one of ordinary skill in the art to practice the invention without the feature of the continuous fluid thickness being lesser than the wavelength of the light being used to irradiate the sample, which is/are critical or essential to the practice of the invention but not included in the claim(s). See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
The specification is clear that their invention is capable of performing a “digital analysis” of an analyte in the sample, wherein a plurality of analytes are emulsified in a plurality of partitions (or droplets) within a single, closed container, and by imaging a set of cross-sections of the closed container. In order to distinguish the signals generated from the crowds of droplets contained so as to perform a digital analysis, the specification explicitly state the below:
“An emulsion is composed of droplets of a first fluid (i.e., dispersed phase) in a second fluid (i.e., continuous phase) that is immiscible with the first fluid. Emulsions are typically cloudy due to scattering of light at surface of the droplets.” (section [0003])
“Clarity of emulsions can be improved by aligning the refractive indices of the immiscible phases, thereby mitigating light scattering effects. Clarity of emulsions can also be improved by forming microemulsions or nanoemulsions in which the characteristic droplet size is less than the wavelength(s) of light being used to irradiate the emulsion (e.g., less than 100 nm).” (section [0003])
“invention(s) can provide methods and systems for forming clear emulsions with droplet sizes greater than wavelengths of light used to interrogate the emulsion for various applications, without requiring matching of the refractive indices of emulsion components (e.g., a dispersed phase and a continuous phase) … In particular, the invention(s) create emulsions with droplets having continuous fluid layers that are much thinner than the wavelength(s) of light being used to irradiate the them, whereby producing clear emulsions without requiring refractive matching for the various fluid/liquid phases used to produce the droplets” (section [0023])
“This feature of the invention is attributed to the thickness of the continuous fluid surrounding each droplet being less than the characteristic wavelength(s) of light used to interrogate the sample” (section [0025])
Because a digital analysis cannot occur in a closed container with a plurality of droplets therein without such a feature1, this feature is an essential element which must be recited in the claims so as to enable the claimed method.
Response to Arguments:
Applicants traverse the rejection.
Applicants contend that the sections to which the Office had cited for the elements for clarity of emulsions being absent in justifying non-enablement (i.e., sections [0003]) is not a requirement as the cited sections employs that the clarity “can be” improved by the discussed means, and that one of skill in the art reading the disclosure would, “first understand that there are multiple means by which clarify of emulsions can be improved, since more than one is mentioned” (page 9, Response).
Applicants also state that that the application-as-filed provides, “ample support of methods that do not include the continuous fluid thickness being lesser than the wavelength of the light being used to irradiate the sample, referring to section [0074] where the specification describes an embodiment of a method 300 for generation of emulsion, where the method includes generating a set of droplets from a sample fluid and generating emulsion upon processing the set of droplets with a set of fluid layers (e.g., to provide a thin film about each droplet) (pages 9 and 10, Response) and the benefits pertaining to generating clear emulsions using multiple continuous fluids (page 10, Response).
These arguments have been carefully considered but they have not been found persuasive.
The inventive concept of the application is based on the ability to take cross-sectional images of a container containing a plurality of droplets therein, wherein each droplet comprises an assay reagent. Because the plurality of droplets comprised in the container are overlapped and closed packed, the method hinges on the clarity of emulsion particles comprised in the container.
Therefore, the enablement is not simply based on being able to provide emulsion particles (or partitions) having clarity, but that which enables the cross-sectional imaging of droplets within the container.
This is clearly discussed in the instant specification where emulsion particles are typically cloudy due to scattering of light surfaces of the droplets:
“An emulsion is composed of droplets of a first fluid (i.e., dispersed phase) in a second fluid (i.e., continuous phase) that is immiscible with the first fluid. Emulsions are typically cloudy due to scattering of light at surface of the droplets.” (section [0003])
And while the specification discloses some means by which the clarity of the emulsion particles can be improved, the discussed means is general in nature and is not related to the method of the invention where the clarity allows for the imaging of the cross-section of a container comprising a plurality of such emulsion droplets (particles).
“Clarity of emulsions can be improved by aligning the refractive indices of the immiscible phases, thereby mitigating light scattering effects. Clarity of emulsions can also be improved by forming microemulsions or nanoemulsions in which the characteristic droplet size is less than the wavelength(s) of light being used to irradiate the emulsion (e.g., less than 100 nm).” (section [0003])
And the specification is clear that the method of improving the clarity of the emulsion that allows for this to occur requires the below elements:
“invention(s) can provide methods and systems for forming clear emulsions with droplet sizes greater than wavelengths of light used to interrogate the emulsion for various applications, without requiring matching of the refractive indices of emulsion components (e.g., a dispersed phase and a continuous phase) … In particular, the invention(s) create emulsions with droplets having continuous fluid layers that are much thinner than the wavelength(s) of light being used to irradiate the them, whereby producing clear emulsions without requiring refractive matching for the various fluid/liquid phases used to produce the droplets” (section [0023])
“This feature of the invention is attributed to the thickness of the continuous fluid surrounding each droplet being less than the characteristic wavelength(s) of light used to interrogate the sample” (section [0025])
Therefore, the Office contends that this enabling element is required, that is, to not only improve the clarity of the emulsion droplets, but the improvement must result in the capability of cross-sections imaging of the plurality of droplets comprised in a container to be made. To this end, such a feature must be claimed.
As to claim 42, the presence of a “film” does not render the claimed invention enabled as a “film” is present on the droplets (or partitions) based on their emulsion condition, but the thickness of such film is what is necessary for the required clarity to be achieved.
The rejection is maintained therefore.
Double Patenting
Rejection – Maintained & New Grounds, Necessitated by Amendment
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 22-41 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 September 16, 2025 is maintained for the reasons of record.
In addition, the rejection of claims 22-41 on the same grounds 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 are maintained for the same reasons of record.
In addition, claims 42-44 are also rejected herein as being necessitated by Amendment (by their addition).
Applicants’ arguments presented in the Amendment received on November 25, 2025 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
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 32).
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 layer3 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.
Response to Arguments:
Applicants traverse the rejection.
Applicants contend that none of the patents of the rejections have claims directed to “performing the digital analysis compris[ing] imaging a set of cross-sections of a container containing the set of partitions using a wavelength of light, wherein the digital analysis for a cell replication cycle stage of the antimicrobial susceptibility test is performed within a duration of three minutes” as recited in claim 22 (page 10, Response).
This argument has not been found persuasive.
Applicants’ attention is directed to claim 1 of the ‘546 patent wherein the claim explicitly recite that the method performs digital analysis involves imaging a set of cross sections of a closed container containing a plurality of partitions within three minutes, and that the analysis pertains to fluorescent signals from labelled target analytes of the sample (claim 4) that necessarily requires a wavelength of light for excitation, and that the partitions being analyzed comprises cell-free nucleic acids.
And while the claims did not explicitly claim that the assay was for an antimicrobial test of a sample, application of digital amplification assay of the ‘546 patent for prior art known analysis that employ digital assay, be it not taking cross-sectional images of a container, such as those disclosed by Jiang et al. (of record) would have been an obvious application of a digital amplification assay, yielding no more than a predictable outcome.
With regard to claim 42, claim the partitions are comprised in oil medium, and therefore would be covered by a film. This is consistent with the disclosure of the 546 patent:
“each fluid layer of the set of fluid layers 150 is immiscible with adjacent fluid layer of the set of fluid layers, wherein at least one of the set of fluid layers is configured to provide a thin film about individual droplets derived from the sample fluid” (column 4, lines 20-23)
With regard to claims 43 and 44, the claimed method of the ‘546 patent necessarily requires the element as discussed above.
Therefore, the invention as claimed is deemed obvious over the claims of the cited patent applications.
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.
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.
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 February 26, 2026
/YJK/
1 Claims 40 also explicitly recite that the method does not require Poisson distribution correction, which also cannot be performed without the subject-critical element.
2 Instant claim 29 was held indefinite, but best possible interpretation is assumed for the purpose of prosecution.
3 The Office assumes that this continuous layer is “fluid” as the claim was rejected under 112, 1st new matter.