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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 July 6, 2026 has been entered.
Preliminary Remark
Claims 3 and 5-20 are canceled.
Rejection – New Grounds, Necessitated by Amendment
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, 2, and 4 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 phrase, “digital PCR emulsion composition has a viscosity of 500 to 5000 mPa.s”. A viscosity of an emulsion composition cannot be defined by itself as the viscosity changes based on it surroundings, such as temperature. Therefore, in the absence of its use and its temperature and surrounding factors, metes and bounds of a viscosity cannot be determined.
Claim 4 is now indefinite because the parent claim already recites that the surfactant comprises HLB having a range of value (2 to 10). Claim 4 reiterates this fact (in fact broadens it by reciting that the surfactant now has a generic “adjustable HLB value”), and the added phrase which requires that the surfactant “does not have an influence on an amplification reaction in PCR” doesn’t further limit the parent claim as a digital PCR emulsion composition having a detergent should not influence the amplification reaction of the contents therein. If such is the case, then it becomes unclear how much “influence” the composition of claim 1 allows, and alternatively, how claim 4 is capable of completely ascertaining that the included surfactant does not (absolutely) influence the amplification reaction occurring in the claimed emulsion particle.
Claims 2 and 4 are indefinite by way of their dependency on claim 1.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 2, and 4 under 35 U.S.C. 103 as being unpatentable over Williamss et al. (Nature Methods, July 2006, vol. 3, no. 7, pages 545-550) in view of Colston et al. (WO 2010/036352 A1, published April 1, 2010) and as evidenced by Nakano et al. (Journal of Biotechnology, 2003, vol. 102, pages 117-124), made in the Office Action mailed on April 8, 2026 is withdrawn in view of the declaration received on June 24, 2026. Specifically, Tween20® (known as polysorbate 20) does not have an HLB values of the claimed range.
Rejection – New Grounds, Necessitated by Amendment
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.
Claims 1, 2, and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Williamss et al. (Nature Methods, July 2006, vol. 3, no. 7, pages 545-550) in view of Khater et al. (Scientific Reports, March 7, 2019, pages 1-11) and as evidenced by Nakano et al. (Journal of Biotechnology, 2003, vol. 102, pages 117-124).
With regard to claim 1, Williams et al., the artisans teach a method composition comprising:
an emulsion formed by mixing PCR sample mixture containing one or two or more amplification target DNAs and a pair of forward and reverse primers, and oil containing a surfactant (“[p]repare the oil-surfactant mixture by thoroughly mixing the following … Span 80 [surfactant] … mineral oil”, page 546; “[t]ransfer 400 ml of the oil-surfactant mixture … [p]repare the aqueous phase for the emulsion by mixing … Forward primer … Reverse primer … dNTPs … Pfu Turbo DNA polymerase … Template DNA … [a]dd 200 ml of the aqueous phase to the oil-surfactant mixture … A w/o emulsion is generated containing approximately 108-109 PCR-competent compartments per milliliter of emulsion”, page 546); and
oil applied on the outside of the emulsion at a uniform thickness (“[p]ipet the emulsion into the wells of a PCR plate as 10 aliquots of 50 ml … Overlay the emulsified and nonemulsified reactions with mineral oil.”, page 547).
The aqueous PCR phase is added at 200 ml to the 400 ml of oil/surfactant mixture, which is a 1:2 in ratio (see page 546, step 2 and page 547, step 4).
With regard to claim 2, the PCR sample mixture further comprises one or two or more from DNA polymerase, dNTP, and a buffer (see above).
With regard to claim 8, Nakano et al. evidence that the method of generating emulsion particles as taught by in a publication having the common artisan, Griffiths, results in microdroplets having the diameter of 2 to 10 mm:
“The W/O emulsion is produced by the following process … Griffiths, 1998 … The prepared W/O emulsion is divided in two … W/O emulsion was observed under microscope …” (page 119, 1st column bottom paragraph to page 119, 2nd column, 1st paragraph)
“The water droplet diameter in the W/O emulsion ranged from 2 to 10 mm” (page 121, 2nd column, 2nd full paragraph)
Williams et al. teach a method of producing emulsion compositions as discussed above. Because the claim only recites the intended usage of the method of the composition for being used in a “digital PCR”, absent an actual application that employs the droplets in a digital PCR employing actively distinct mechanisms different from those disclosed by Williams et al., the limitation claims are met.
Williams et al., while explicitly teaching that the surfactant is a non-ionic surfactant, known as SPAN 80, do not explicitly teach that the surfactant is sorbitan monolaurate having an HLB value of 2 to 10.
Khater et al. teach a well-known means of generating emulsion particles comprising PCR substrates therein in an immiscible fluid comprising a surfactant, in particular, Span20, wherein the artisans study the effects of adding SPAN20 to the carrier phase (i.e., oil or immiscible carrier fluid surrounding the aqueous PCR droplet):
“the effect of adding SPAN 20 to the carrier phase on the size and stability of droplets was investigated” (page 3, 1st paragraph)
The artisans, upon the study conclude that the addition of SPAN 20 results in the reduction of the interfacial tension between the immiscible phrases and improves the stability of droplets at higher temperatures due to the increase in the resistance of water droplets against coalescence (page 3, 2nd and 3rd paragraph).
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 combine the teachings of Williams et al. and Khater et al. and Nakano et al., thereby arriving at the invention as claimed for the following reasons.
The motivation to combine the teachings of Williams et al. and Khater et al. is expressly provided by Khater et al. who demonstrate that he addition of surfactant, SPAN 20 results in the increase of stability in emulsion droplets (especially during high temperatures involved in PCR), that circumvents coalescence of emulsion droplets which would result in deleterious outcome.
“adding SPAN20 surfactant improves the stability of droplets at higher temperatures mainly due to the increase in the resistance of water droplets against coalescence … increasing the temperature decreases the distance between successive droplets. This distance in the absence of surfactants reduces dramatically and increases the risk of droplets coalescence (the coalescence of droplets is observed at 90 °C). The droplets flowing over the heater remain stable in the presence of surfactant at even 100 °C temperature. As a result of the instability of droplets at high temperatures in the absence of surfactants …” (page 3)
Therefore, while Williams et al. did not employ sorbitan monolaurate, such as SPAN20 with the immiscible fluid (i.e., oil) when generating their PCR emulsion products, one of ordinary skill in the art would have been well-aware of other combinations of surfactants which could be combined with the immiscible fluid when generating emulsified droplets for performing PCR.
In addtiion, Khater et al. specifically teach the benefit of adding Span 20 in the carrier immiscible fluid surrounding the emulsion particle, providing the motivation to do so.
With regard to the HLB value the surfactant being between 2 to 10, SPAN20 is known to possess an HLB value of 7-9 (see attached product description from esteem-india.com).
With regard to the viscosity, while the limitation has been deemed indefinite, because the surfactant employed by Khater et al. is identical to that which was employed by applicants, the limitation is assumed to be inherent.
For these reasons, the invention as claimed is deemed prima facie obvious over the cited references.
Conclusion
No claims are allowed.
Applicant’s arguments with respect to the previous rejection have been considered but are moot in view of the new ground of rejection based on Khater et al.
The Office also notes that Regev et al. (WO 2016/138488 A1, published September 2016) discuss that ability of various surfactants that includes SPAN 20 and its ability to stabilize emulsion particles when added to its carrier fluid (see section [00162], “Furthermore, the surfactant can serve to stabilize aqueous emulsions in fluorinated oils from coalescing. Droplets may be surrounded by a surfactant which stabilizes the droplets by reducing the surface tension at the aqueous oil interface. Preferred surfactants that may be added to the carrier fluid include, but are not limited to, surfactants such as sorbitan- based carboxylic acid esters (e.g., the "Span" surfactants, Fluka Chemika), including sorbitan monolaurate (Span 20), sorbitan monopalmitate (Span 40), sorbitan monostearate (Span 60) and sorbitan monooleate (Span 80), and perfluorinated polyethers (e.g., DuPont Krytox 157 FSL, FSM, and/or FSH).”
The document, is excessive in number of pages and will not be provided herewith. However, the document is available via patents.google.com.
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 September 5, 2026
/YJK/
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