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 .
Status of the Application
Claims 1-20 are pending and under examination
The following Office Action is in response to Applicant's communication dated 02/20/2024.
Claim Rejections - 35 USC § 112(b)
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.
Claim(s) 6 and 10 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 6 recites “correlating between the plurality of images and a largest diameter of the identified droplets”, which renders the claim indefinite because the language does not clearly define what is being correlated or how the correlation is performed. Additionally, “identified droplets” plural at the beginning of the claim conflicts with “identified droplet” singular later in the claim. It is unclear whether the volumes are determined for one or multiple droplets.
Claim 10 recites “fitting a curve to a circle diameter of the identified droplets; and interpolating the largest diameter from the curve.”, which renders the claim indefinite because a “circle diameter” is not a curve to which a curve is ordinarily fit, and the claim does not reasonably specify what curve is fitted or how interpolation from that curve determines the largest diameter. For purposes of examination only, and to facilitate a complete analysis of the claim, the Examiner interprets the “fitting a curve to a circle diameter of the identified droplets; and interpolating the largest diameter from the curve.” As requiring automated image process step in which detected droplet boundary pixels are fitted with a best-fit circle, and the radius/diameter of the fitted circle is used to determine the diameter of detected droplet. In this interpretation, the claimed “curve” corresponds to the fitted circle. This interpretation is consistent with Applicant’s specification [¶0200, ¶0326-0331]. This interpretation is adopted solely for examination and does not resolve the lack of clarity in the claim language.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 5, 7-9, 12, and 18-20 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Colston et al. ( US9156010B2, EFD: September 23rd 2009)
Regarding claim 1, Colston discloses a method for performing a digital assay, the method comprising: producing a plurality of polydisperse droplets, wherein at least some droplets of the plurality of polydisperse droplets comprise a sample, the sample comprising a target molecule; (e.g. droplet generation 504 comprising encapsulating the nucleic acids in droplets, for example, with about one copy of each target nucleic acid per droplet, where the droplets are suspended in an immiscible carrier fluid, such as oil, to form an emulsion. [¶0139 and Fig. 1]. Droplets may be polydisperse [¶0144].)
amplifying the sample to produce an amplified product; (e.g. Reaction 506 may involve subjecting the droplets to a suitable reaction, such as thermal cycling to induce PCR amplification, so that target nucleic acids, if any, within the droplets are amplified to form additional copies [¶0139 and Fig. 1])
associating the amplified product with a detectable agent; detecting a presence or absence of the
amplified product and the detectable agent in droplets of the plurality of droplets to identify droplets comprising the amplified product and the detectable agent or the target molecule; (e.g. In some embodiments, reaction comprise at least one probe and/or dye to enable detection of amplification [¶0159]. Detection 508 may involve detecting some signal(s) from the droplets indicative of whether or not there was amplification. [¶0139 and Fig. 1]).
determining the concentration of the target molecule in the sample based on a volume of the sample and a number of the identified droplets comprising the amplified product and the detectable agent. (e.g. data analysis 510 may involve estimating a concentration of the target nucleic acid (, i.e., the number of target molecules per unit volume) in the sample based on the percentage of droplets in which amplification occurred. [¶0139, ¶0944 and Fig. 1]).
Regarding claim 2, Colston discloses measuring volumes of the identified droplets comprising the amplified product and the detectable agent, wherein determining the concentration of the target molecule in the sample is further based on the volumes of the identified droplets comprising the amplified product and the detectable agent. (e.g. The detection of droplets include determining volume [¶0837]. Target molecule concentration depends on the number of target molecules and the volume of each droplet, determining the target concentration generally also involves determination of the volume distribution of the droplets [¶0945].)
Regarding claims 5, 7 and 8, Colston discloses obtaining an image stack, which comprises optical imaging, of the plurality of polydisperse droplets, wherein the image stack comprises a plurality of images from a plurality of focal planes; wherein detecting a presence or absence of the amplified product and the detectable agent in droplets of the plurality of droplets comprises using the plurality of the images. (e.g. optical detection system, which detect fluorescence from sample-containing droplets. The system comprises chambers 4568, 4570, which may have a relatively shallow depth, to allow substantially only a monolayer of droplets within each chamber, so that only one droplet is disposed within each portion of the line of sight of a detector and is confined to the focal plane of the detector. Alternatively, various three-dimensional detection configurations, such as confocal imaging or wide-field imaging with deconvolution, may be used with non-monolayer samples. [¶0898-0901].)
Regarding claim 9, Colston discloses measuring the volumes comprises determining a largest diameter of the identified droplets. (e.g. in scatter detector, if this width is less than the diameter of channel 4214, then it can be inferred that the droplet is an approximate sphere with a diameter less than the diameter of channel 4214, and the volume of the droplet can be calculated.[¶0847]).
Regarding claim 12. Colston discloses the target molecule is selected from the group consisting of a nucleic acid molecule, a polypeptide, and a lipid. (e.g. the components of interest within the samples—a nucleic acid, an enzyme, a virus, a bacterium, etc. [¶0013])
Regarding claim 13. Colston discloses amplification comprises performing PCR, RCA, LAMP, etc. [¶0164].
Regarding claim 18, Colston discloses volumes of the plurality of polydisperse droplets vary by more than a factor of about 2, more than a factor of about 10, or by more than a factor of about 100. (e.g. the volume of droplets may be between about one microliter and one nanoliter or between about one microliter and one picoliter, between about one nanoliter and one picoliter, or between about one picoliter and one femtoliter[¶0149]. These disclosed volume ranges correspond to volume variations greater than 2, 10, or 100.)
Regarding claims 19 and 20, Colston discloses droplets further comprises a fluid interface modification element (e.g. surfactant) [¶0145]
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.
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.
Colston et al. and Baret et al.
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Colston et al. ( US9156010B2, EFD: SEPTEMBER 23RD 2009) in view of Baret et al. (Lab Chip 2009; 9 (13): 1850–1858).
Regarding claim 3, Colston does not discloses the method does not comprise measuring volumes of any droplets of the plurality of polydisperse droplets determined not to comprise the amplified product and the detectable agent or target molecule.
Baret discloses that after fluorescence detection, positive droplets can be selectively processed downstream while non-florescence/negative droplets are sent to waste. [pages 1856-1857].
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to avoid measuring volume of negative droplets in order to enrich and further process only the desired subpopulations of droplets according to their fluorescence [Baret, page 1850], hence avoid analysis burden and focus computational capacity on droplets contributing to the target positive concentration determination. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (MPEP § 2143).
Colston et al.
Claim(s) 9, 16, and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Colston et al. ( US9156010B2, EFD: SEPTEMBER 23RD 2009)
Regarding claim 9, Colston discloses the detection of droplets themselves include determining droplet size (e.g., radius) [¶0837]. The reference further discloses droplets typically with a spherical shape [¶0149]. Although Colston does not explicitly say measuring the volumes by determining diameter, a skilled artisan would have been able to calculate volume of droplet from radius/diameter measurement by multiplying radius by equation volume = (4/3)πr³.
Regarding claims 16 and 17, Colston does not explicitly discloses a distribution of droplet diameters as a percentage of mean and/or median, but Colston discloses droplets are often spherical shape (characterized by diameter/radius and volume) of various sizes or may vary in size with predetermined or random size distribution [¶0149, ¶0915, ¶0946]. Colston further discloses that when droplet volume varies significantly, concentration maybe calculated for a given droplet size distribution, including Gaussian distribution of droplet volumes characterized by mean and standard deviation of droplet volume [¶0987]. One of ordinary skill in the art would have known that spherical droplets volume and diameter/radius are mathematically related using function of Volume=(4/3)πr³ or Volume= πd³/6 (r is radius and d is diameter) so droplet volume is cube is proportional to the cube of droplet diameter. For instant, Colston’s 100% volume standard deviation [0144] corresponds to 33% diameter standard deviation. It would have been obvious to one of ordinary skill in the art to characterize Colston’s droplets using standard deviation relative to mean or median droplet diameter because mean, median, and standard deviation are conventional ways to describe size distribution, and Colston expressly teaches non-uniform droplet size distribution. Accordingly, selecting a droplet population having a diameter standard deviation greater than the claimed percentages is routine optimization on degree of polydispersity, a result-effective variable regcognized by Colston. See MPEP § 2144.05 (II) "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Colston et al. and Brás et al.
Claim(s) 10 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Colston et al. ( US9156010B2, EFD: SEPTEMBER 23RD 2009) and Brás et al. (Int. J. Chem. Eng. 2009. 10.1155/ 746439.)
Regarding claims 10 and 11, Colston discloses the detection of droplets themselves include determining droplet size (e.g., radius) [¶0837]. However, Colston did not go into detail on the process of acquiring the measurements from detectable data, such as detecting the boundary of droplets and fitting boundary of interest with a best-fit circle for determining droplet size.
Brás discloses measurement technique of drop size distribution. The process for the detection of the drops in an image has two distinct steps. In the first step, they detect the edges of the drops in the original image by monitoring the values of the gradient and the descending thickness and by creating an output image with those contours. In the second phase, we detect the drops in this contour image, using the Hough Transform, a widely used in image processing to detect lines, circles, and calculates their parameters (e.g. radius, diameters).
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to use Brás’ image processing technique of detecting droplet boundaries and apply Hough Transform/best fit circle to determine droplet radius because the combination provide an automated objective, and reproducible way to extract droplet radius, thereby enable calculation of volume in determining concentration of analytes. Colton already teaches detecting droplet size including radius for spherical droplets. Brás teaches a known way to calculate of particle size using Colston’s own data.
Colston et al. and Invitrogen
Claim(s) 14 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Colston et al. ( US9156010B2, EFD: SEPTEMBER 23RD 2009) and Invitrogen (Invitrogen. (2008). ELISA Amplification System Instruction Manual.)
Regarding claims 14 and 15, Colston does not disclose amplification comprises antibody-based amplification (e.g. ELISA Amplification System).
Invitrogen discloses ELISA Amplification System.
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to substitute Colston’s amplification method(s) with Invitrogen’s ELISA Amplification System because ELISA Amplification System is designed as a merge between generic PCR with the high-throughput, colorimetric detection of an ELISA. This hybrid allows higher sensitivity [pages 2-3]. This combination represents predictable substitution of one known amplification method for another known amplification method with reasonable expectation of success with motivation of acquiring higher sensitivity for amplification assay. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (MPEP § 2143, B and D).
Double Patenting
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.
U.S. Patent No. 10,619,192 B2
Claim(s) 1, 2, 4-8, 13, 17-20 rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1, 3- 9, 11, 12, 17, 20, 21 of U.S. Patent No. 10619192B2 (the ‘192 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding present claim(s) 1, the claim of the ‘192 patent discloses method for performing a digital assay, the method comprising: producing a plurality of polydisperse droplets, wherein at least some droplets of the plurality of polydisperse droplets comprise a sample, the sample comprising a target molecule; amplifying the sample to produce an amplified product; associating the amplified product with a detectable agent; detecting a presence or absence of the amplified product and the detectable agent in droplets of the plurality of droplets to identify droplets comprising the amplified product and the detectable agent or the target molecule; and determining the concentration of the target molecule in the sample based on a volume of the sample and a number of the identified droplets comprising the amplified product and the detectable agent. (e.g. as per claim(s) 1 and 8 of the ‘192 patent).
Regarding present claim(s) 2, the claim of the ‘192 patent discloses measuring volumes of the identified droplets comprising the amplified product and the detectable agent, wherein determining the concentration of the target molecule in the sample is further based on the volumes of the identified droplets comprising the amplified product and the detectable agent. (e.g. as per claim(s) 1 and 8 of the ‘192 patent).
Regarding present claim(s) 4, the claim of the ‘192 patent discloses obtaining an image stack of the plurality of polydisperse droplets, wherein the image stack comprises a plurality of images from a plurality of focal planes; wherein measuring the volumes of the identified droplets comprising the amplified product and the detectable agent comprises using the plurality of the images. (e.g. as per claim(s) 1, 8 and 9 of the ‘192 patent).
Regarding present claim(s) 5, the claim of the ‘192 patent discloses obtaining an image stack of the plurality of polydisperse droplets, wherein the image stack comprises a plurality of images from a plurality of focal planes; wherein detecting a presence or absence of the amplified product and the detectable agent in droplets of the plurality of droplets comprises using the plurality of the images. (e.g. as per claim(s) 1, 8 and 9 of the ‘192 patent).
Regarding present claim(s) 6, the claim of the ‘192 patent discloses measuring the volumes of the identified droplets further comprises: correlating between the plurality of images and a largest diameter of the identified droplets; and determining the volumes of the identified droplet therefrom. (e.g. as per claim(s) 11 and 12 of the ‘192 patent).
Regarding present claim(s) 7, the claim of the ‘192 patent discloses obtaining the image stack comprises optical imaging. (e.g. as per claim(s) 20 and 21 of the ‘192 patent).
Regarding present claim(s) 8, the claim of the ‘192 patent discloses detecting a presence or absence of the amplified product and the detectable agent comprises optical imaging. (e.g. as per claim(s) 20 of the ‘192 patent).
Regarding present claim(s) 13, the claim of the ‘192 patent discloses amplifying the sample comprises comprises performing polymerase chain reaction (PCR), rolling circle amplification (RCA), nucleic acid sequence based amplification (NASBA), loop-mediated amplification (LAMP), strand displacement amplification, helicase-dependent amplification, circular helicase-dependent amplification, transcription mediated amplification (TMA), self-sustained sequence replication (3SR), and single primer isothermal amplification (SPIA), signal mediated amplification of RNA technology (SMART), branched rolling circle amplification (HRCA), exponential amplification reaction (EXPAR), smart amplification (SmartAmp), isothermal and chimeric primer-initiated amplification of nucleic acids (ICANS), and multiple displacement amplification (MDA), isothermal multiple displacement amplification, or a combination thereof. (e.g. as per claim(s) 5 of the ‘192 patent).
Regarding present claim(s) 17, the claim of the ‘192 patent discloses a distribution of droplet diameters of the plurality of polydisperse droplets comprises a standard deviation greater than 100%, greater than 50%, greater than 30%, greater than 20%, greater than 15%, greater than 10%, greater than 9%, greater than 8%, greater than 7%, greater than 6%, or greater than 5% of the mean droplet diameter. (e.g. as per claim(s) 6 of the ‘192 patent).
Regarding present claim(s) 18, the claim of the ‘192 patent discloses volumes of the plurality of polydisperse droplets vary by more than a factor of about 2, more than a factor of about 10, or by more than a factor of about 100. (e.g. as per claim(s) 7 of the ‘192 patent).
Regarding present claim(s) 19, the claim of the ‘192 patent discloses the plurality of polydisperse droplets further comprises a fluid interface modification element. (e.g. as per claim(s) 3 and 17 of the ‘192 patent).
Regarding present claim(s) 20, the claim of the ‘192 patent discloses the fluid interface modification element is a surfactant. (e.g. as per claim(s) 4 and 18 of the ‘192 patent).
U.S. Patent No. 11,427,857 B2
Claim(s) 1, 2, 4-6, 8-18 rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-3, 5-11, 13-16 of U.S. Patent No. 11427857B2 (the ‘857 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding present claim(s) 1, the claim of the ‘857 patent discloses method for performing a digital assay, the method comprising: producing a plurality of polydisperse droplets, wherein at least some droplets of the plurality of polydisperse droplets comprise a sample, the sample comprising a target molecule; amplifying the sample to produce an amplified product; associating the amplified product with a detectable agent; detecting a presence or absence of the amplified product and the detectable agent in droplets of the plurality of droplets to identify droplets comprising the amplified product and the detectable agent or the target molecule; and determining the concentration of the target molecule in the sample based on a volume of the sample and a number of the identified droplets comprising the amplified product and the detectable agent. (e.g. as per claim(s) 1 and 16 of the ‘857 patent).
Regarding present claim(s) 2, the claim of the ‘857 patent discloses measuring volumes of the identified droplets comprising the amplified product and the detectable agent, wherein determining the concentration of the target molecule in the sample is further based on the volumes of the identified droplets comprising the amplified product and the detectable agent. (e.g. as per claim(s) 1 of the ‘857 patent).
Regarding present claim(s) 4, the claim of the ‘857 patent discloses obtaining an image stack of the plurality of polydisperse droplets, wherein the image stack comprises a plurality of images from a plurality of focal planes; wherein measuring the volumes of the identified droplets comprising the amplified product and the detectable agent comprises using the plurality of the images. (e.g. as per claim(s) 5-6 of the ‘857 patent).
Regarding present claim(s) 5, the claim of the ‘857 patent discloses obtaining an image stack of the plurality of polydisperse droplets, wherein the image stack comprises a plurality of images from a plurality of focal planes; wherein detecting a presence or absence of the amplified product and the detectable agent in droplets of the plurality of droplets comprises using the plurality of the images. (e.g. as per claim(s) 5-6 of the ‘857 patent).
Regarding present claim(s) 6, the claim of the ‘857 patent discloses measuring the volumes of the identified droplets further comprises: correlating between the plurality of images and a largest diameter of the identified droplets; and determining the volumes of the identified droplet therefrom. (e.g. as per claim(s) 5-7 of the ‘857 patent).
Regarding present claim(s) 8, the claim of the ‘857 patent discloses detecting a presence or absence of the amplified product and the detectable agent comprises optical imaging. (e.g. as per claim(s) 1 of the ‘857 patent).
Regarding present claim(s) 9, the claim of the ‘857 patent discloses measuring the volumes of the identified droplets comprising the amplified product and the detectable agent or the target molecule comprises determining a largest diameter of the identified droplets. (e.g. as per claim(s) 1 of the ‘857 patent).
Regarding present claim(s) 10, the claim of the ‘857 patent discloses determining the largest diameter of the identified droplets comprises: fitting a curve to a circle diameter of the identified droplets; and interpolating the largest diameter from the curve. (e.g. as per claim(s) 2 of the ‘857 patent).
Regarding present claim(s) 11, the claim of the ‘857 patent discloses determining the largest diameter of the identified droplets comprises determining a boundary of the droplet. (e.g. as per claim(s) 3 of the ‘857 patent).
Regarding present claim(s) 12, the claim of the ‘857 patent discloses the target molecule is selected from the group consisting of a nucleic acid molecule, a polypeptide, and a lipid. (e.g. as per claim(s) 8 of the ‘857 patent).
Regarding present claim(s) 13, the claim of the ‘857 patent discloses amplification comprises performing polymerase chain reaction (PCR), rolling circle amplification (RCA), nucleic acid sequence based amplification (NASBA), loop-mediated amplification (LAMP), strand displacement amplification, helicase-dependent amplification, circular helicase-dependent amplification, transcription mediated amplification (TMA), self-sustained sequence replication (3SR), and single primer isothermal amplification (SPIA), signal mediated amplification of RNA technology (SMART), branched rolling circle amplification (HRCA), exponential amplification reaction (EXPAR), smart amplification (SmartAmp), isothermal and chimeric primer-initiated amplification of nucleic acids (ICANS), and multiple displacement amplification (MDA), isothermal multiple displacement amplification, or a combination thereof. (e.g. as per claim(s) 9 of the ‘857 patent).
Regarding present claim(s) 14, the claim of the ‘857 patent discloses amplification comprises performing antibody-based amplification. (e.g. as per claim(s) 10 of the ‘857 patent).
Regarding present claim(s) 15, the claim of the ‘857 patent discloses amplification comprises performing digital ELISA. (e.g. as per claim(s) 11 of the ‘857 patent).
Regarding present claim(s) 16, the claim of the ‘857 patent discloses a distribution of droplet diameters of the plurality of polydisperse droplets comprises a standard deviation greater than 100%, greater than 50%, greater than 30%, greater than 20%, greater than 15%, greater than 10%, greater than 9%, greater than 8%, greater than 7%, greater than 6%, or greater than 5% of the median droplet diameter. (e.g. as per claim(s) 13 of the ‘857 patent).
Regarding present claim(s) 17, the claim of the ‘857 patent discloses a distribution of droplet diameters of the plurality of polydisperse droplets comprises a standard deviation greater than 100%, greater than 50%, greater than 30%, greater than 20%, greater than 15%, greater than 10%, greater than 9%, greater than 8%, greater than 7%, greater than 6%, or greater than 5% of the mean droplet diameter. (e.g. as per claim(s) 14 of the ‘857 patent).
Regarding present claim(s) 18, the claim of the ‘857 patent discloses volumes of the plurality of polydisperse droplets vary by more than a factor of about 2, more than a factor of about 10, or by more than a factor of about 100. (e.g. as per claim(s) 15 of the ‘857 patent).
U.S. Patent No. 11,939,626 B2
Claim(s) 1, 2, 4-8, 13, 14, 17-20 rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1, 3-10, 14, 16, 18 of U.S. Patent No. 11939626B2 (the ‘626 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding present claim(s) 1, the claim of the ‘626 patent discloses method for performing a digital assay, the method comprising: producing a plurality of polydisperse droplets, wherein at least some droplets of the plurality of polydisperse droplets comprise a sample, the sample comprising a target molecule; amplifying the sample to produce an amplified product; associating the amplified product with a detectable agent; detecting a presence or absence of the amplified product and the detectable agent in droplets of the plurality of droplets to identify droplets comprising the amplified product and the detectable agent or the target molecule; and determining the concentration of the target molecule in the sample based on a volume of the sample and a number of the identified droplets comprising the amplified product and the detectable agent. (e.g. as per claim(s) 1 and 16 of the ‘626 patent).
Regarding present claim(s) 2, the claim of the ‘626 patent discloses measuring volumes of the identified droplets comprising the amplified product and the detectable agent, wherein determining the concentration of the target molecule in the sample is further based on the volumes of the identified droplets comprising the amplified product and the detectable agent. (e.g. as per claim(s) 1 and 16 of the ‘626 patent).
Regarding present claim(s) 4, the claim of the ‘626 patent discloses obtaining an image stack of the plurality of polydisperse droplets, wherein the image stack comprises a plurality of images from a plurality of focal planes; wherein measuring the volumes of the identified droplets comprising the amplified product and the detectable agent comprises using the plurality of the images. (e.g. as per claim(s) 1 and 16 of the ‘626 patent).
Regarding present claim(s) 5, the claim of the ‘626 patent discloses obtaining an image stack of the plurality of polydisperse droplets, wherein the image stack comprises a plurality of images from a plurality of focal planes; wherein detecting a presence or absence of the amplified product and the detectable agent in droplets of the plurality of droplets comprises using the plurality of the images. (e.g. as per claim(s) 1, 9, and 16 of the ‘626 patent).
Regarding present claim(s) 6, the claim of the ‘626 patent discloses measuring the volumes of the identified droplets further comprises: correlating between the plurality of images and a largest diameter of the identified droplets; and determining the volumes of the identified droplet therefrom. (e.g. as per claim(s) 10 and 18 of the ‘626 patent).
Regarding present claim(s) 7, the claim of the ‘626 patent discloses obtaining the image stack comprises optical imaging. (e.g. as per claim(s) 14 and 16 of the ‘626 patent).
Regarding present claim(s) 8, the claim of the ‘626 patent discloses detecting a presence or absence of the amplified product and the detectable agent comprises optical imaging. (e.g. as per claim(s) 14 of the ‘626 patent).
Regarding present claim(s) 13, the claim of the ‘626 patent discloses amplification comprises performing polymerase chain reaction (PCR), rolling circle amplification (RCA), nucleic acid sequence based amplification (NASBA), loop-mediated amplification (LAMP), strand displacement amplification, helicase-dependent amplification, circular helicase-dependent amplification, transcription mediated amplification (TMA), self-sustained sequence replication (3SR), and single primer isothermal amplification (SPIA), signal mediated amplification of RNA technology (SMART), branched rolling circle amplification (HRCA), exponential amplification reaction (EXPAR), smart amplification (SmartAmp), isothermal and chimeric primer-initiated amplification of nucleic acids (ICANS), and multiple displacement amplification (MDA), isothermal multiple displacement amplification, or a combination thereof. (e.g. as per claim(s) 5 of the ‘626 patent).
Regarding present claim(s) 14, the claim of the ‘626 patent discloses amplification comprises performing antibody-based amplification. (e.g. as per claim(s) 6 of the ‘626 patent).
Regarding present claim(s) 17, the claim of the ‘626 patent discloses a distribution of droplet diameters of the plurality of polydisperse droplets comprises a standard deviation greater than 100%, greater than 50%, greater than 30%, greater than 20%, greater than 15%, greater than 10%, greater than 9%, greater than 8%, greater than 7%, greater than 6%, or greater than 5% of the mean droplet diameter. (e.g. as per claim(s) 7 and 16 of the ‘626 patent).
Regarding present claim(s) 18, the claim of the ‘626 patent discloses volumes of the plurality of polydisperse droplets vary by more than a factor of about 2, more than a factor of about 10, or by more than a factor of about 100. (e.g. as per claim(s) 8 of the ‘626 patent).
Regarding present claim(s) 19, the claim of the ‘626 patent discloses the plurality of polydisperse droplets further comprises a fluid interface modification element. (e.g. as per claim(s) 3 of the ‘626 patent).
Regarding present claim(s) 20, the claim of the ‘626 patent discloses the fluid interface modification element is a surfactant. (e.g. as per claim(s) 4 of the ‘626 patent).
Allowable Subject Matter
Claims 4 and 6 are free of prior art, but objected to as being dependent upon a rejected base claim. The following references were considered as the closest prior arts:
Colston et al. ( US9156010B2, EFD: SEPTEMBER 23RD 2009) teaches the limitations of claims 1 and 2, upon which claims 4 and 6 depend, as discussed above in 35 USC § 102 rejection section.
Penfold et al. (Langmuir 22.5 (2006): 2005-2015, disclosed in IDS), teaches obtaining an image stack of a droplet is known in the art (e.g. fluorescent dye Nile Red as in section 2.1, pg. 2006; obtaining image stacks as in section 2.2, pg. 2006-2007; Fig. 1, pg.2008; Section 4.1, Results and Discussion section, pg. 2009-2010; 2nd para, Section 4.2, pg. 2010-2011; Fig. 3, pg. 2010).
However, the prior art does not teach or fairly suggest the claimed combination of steps including obtaining an image stack of the plurality of polydisperse droplets, wherein the image stack comprises a plurality of images from a plurality of focal planes; and measuring a volume of a droplet of the plurality of polydisperse droplets using the plurality of the images.
Conclusion
No claims are allowed
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/KHAI QUYNH TIEN PHAM/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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