DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
Claim(s) 20, 21, 23, 24, 26-35 is/are rejected under pre-AIA 35 U.S.C. 102(e) as being anticipated by Anderson (US 2004/0180346, IDS ref).
Regarding claim 20, Anderson disclosed:
A method for analyzing a sample,
For example, see Abstract: “Another embodiment of the invention provides a system for nucleic acid amplification and detection of a sample comprising partitioning the sample into partitioned sections, performing PCR on the partitioned sections of the sample, and detecting and analyzing the partitioned sections of the sample.”
comprising: (a) supplying a continuous flow of a carrier fluid;
Figure 3, paragraph 0037: “The microdroplets 308 suspended in an immiscible carrier fluid 314 are pumped through the continuous tube 309 by pump 311.”
(b) introducing a sample which is immiscible with said carrier fluid into said flow of said carrier fluid to thereby form a plurality of droplets of said sample enveloped in said carrier fluid;
Figure 3 and paragraph 0036: “The sample and a PCR reagent are injected through a small orifice 306. The injection of the sample through the small orifice 306 produces microdroplets 308.”
(c) controlling the flow of said sample and/or said carrier fluid such that said sample remains enveloped in said carrier fluid;
Figure 3 and paragraph 0037: “The microdroplets 308 suspended in an immiscible carrier fluid 314 are pumped through the continuous tube 309 by pump 311. The microdroplets 308 suspended in an immiscible carrier fluid 314 are cycled through heater 310 and cooler 315 to perform PCR.”
and (d) analyzing said plurality of droplets while enveloped within said carrier fluid to determine a presence or absence of a target analyte in said sample.
Figure 3 and paragraph 0038: “The detection and analysis section 303 includes a blue laser 312 and a detector 313. The laser 312 is projected upon the droplets 308 as they pass through tube 308 between the laser 312 and the detector 313.” Also paragraph 0033: “The partitioned portions of the sample are optically probed to detect the colorimetric indicator which signals the presence of the target DNA.”
Regarding claim 21, see paragraph 0039: “the immiscible fluid 314, such as mineral oil”.
Regarding claims 23 and 24, see paragraph 0037: “The microdroplets 308 suspended in an immiscible carrier fluid 314 are cycled through heater 310 and cooler 315 to perform PCR.”
Regarding claims 26 and 27, see paragraph 0038: “The detection and analysis section 303 includes a blue laser 312 and a detector 313. The laser 312 is projected upon the droplets 308 as they pass through tube 308 between the laser 312 and the detector 313.” Also paragraph 0033: “The partitioned portions of the sample are optically probed to detect the colorimetric indicator which signals the presence of the target DNA.”
Regarding claims 28 and 29, see paragraph 0039: “An optical signal (e.g., fluorescence or optical absorption), generated by degradation of the dye/quencher pair on the primer, is detected using a confocal imaging system such as that employed in conventional flow cytometers.”
Regarding claims 30 and 31, see paragraph 0038: “The detection and analysis section 303 includes a blue laser 312 and a detector 313. The laser 312 is projected upon the droplets 308 as they pass through tube 308 between the laser 312 and the detector 313.” Also paragraph 0033: “The partitioned portions of the sample are optically probed to detect the colorimetric indicator which signals the presence of the target DNA.”
Regarding claim 32, it is unclear whether the term “stage” refers to a “step” or a “location”. If referring to a “step”, Anderson disclosed (Figure 2) PCR prior to detection. If referring to a location, as seen in Figure 3, this would depend on one’s point of reference, since the path through the heater 310, cooler 315, and detector 313 is circuitous. Depending on the direction of flow (clockwise or counterclockwise) and an arbitrarily chosen “beginning” of the path, the detector would be “after” the thermal cycling stage.
Regarding claims 33 and 34, see paragraph 0033: “The partitioned portions of the sample are optically probed to detect the colorimetric indicator which signals the presence of the target DNA.”
Regarding claim 35, Anderson disclosed partitioning the sample into droplets (e.g. paragraph 0019). This would separate the target nucleic acid from “the sample”.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claim 22 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Anderson (US 2004/0180346, IDS ref) in view of Corbett (US 5,270,183, IDS ref).
The teachings of Anderson have been discussed. While Anderson taught mineral oil, he did not teach silicone oil.
Corbett also taught a continuous flow reaction system where a sample surrounded by immiscible carrier fluid flowed through the system (abstract). Corbett taught the carrier fluid could be mineral oil or silicone oil (column 7, lines 36-39).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the method of Anderson by substituting mineral oil with silicone oil, as Corbett taught both types of oil for the same purpose as Anderson’s mineral oil. Per MPEP 2144.06, it is prima facie obvious to substitute equivalents known for the same purpose.
Claim 25 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Anderson (US 2004/0180346, IDS ref) in view of Matthies (US 2002/0060156, IDS ref).
The teachings of Anderson have been discussed. Anderson did not teach that the temperature ramping gradient (i.e. the rate of temperature change) was between 17 °C/sec and 25 °C/sec.
Matthies taught that microfabrication of PCR devices conferred the advantage of rapid temperature cycling; paragraph 0100: “One major advantage of a microfabricated PCR device is the ability to do fast thermal cycling. A portion of a typical temperature profile recorded for a glass PCR-CE device is shown in FIG. 4. Heating rates in this case are 20° C./sec whilst cooling rates are 2° C./sec.”
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to fabricate the device of Anderson on a scale and of a material to achieve the rapid thermal cycling noted by Matthies, as this would have offered the advantage of shorter cycling times and therefore faster results.
Claims 36 and 37 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Anderson (US 2004/0180346, IDS ref) in view of Giesing (US 7,056,660, IDS ref).
The teachings of Anderson have been discussed. Anderson did not disclose using the device to analyze “rare mutated cells from a sample of bodily fluid or tissue”, or that the analysis was “configured to target cells that occur about one part in 106.
Giesing disclosed (column 9, lines 31-35): “In a particular embodiment of the present invention, single cancer cells are removed from the body fluid and are also investigated singly. It is possible for this purpose to analyse an altered genome of a single degenerate cell by genome amplification by a so-called single-cell PCR.” Note that a “single cancer cell” would certainly represent less than one part in 106 in a person.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use Anderson’s device to amplify and detect nucleic acid from the cells isolated by Giesing, because Anderson’s device offered an advantage over other PCR/detection technologies. Anderson disclosed (paragraph [0025]): “The system 100 has significant advantages over typical bulk DNA detection techniques (even microscale bulk solution approaches), including (1) much faster detection time through a reduction in the total number of temperature cycles required, (2) a reduction in the time for each cycle, and (3) removing interference from competing DNA templates. The system 100 achieves a reduction in the total number of cycles by limiting the dilution of the optically generated signal (e.g., fluorescence or absorption). The formation of partitioned fluid volumes of the DNA-containing solution effectively isolates the fluid volumes which contain the target DNA from the fluid volumes that do not contain the target DNA. Therefore, the dilution of the optical signal is largely eliminated, allowing much earlier detection.”
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.
Claims 20, 23, 24, 26, 27, 31-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 9,631,230. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘230 claims disclose:
Regarding instant claim 20:
A method for analyzing a sample, comprising: (a) supplying a continuous flow of a carrier fluid;
Claim 1: “provide a set of sample droplets in a continuous flow of immiscible carrier fluid through a channel”.
(b) introducing a sample which is immiscible with said carrier fluid into said flow of said carrier fluid to thereby form a plurality of droplets of said sample enveloped in said carrier fluid;
Claim 1: “providing at least one starting sample comprising at least one nucleic acid; segmenting at least part of the at least one starting sample to provide a set of sample droplets in a continuous flow of immiscible carrier fluid through a channel”.
(c) controlling the flow of said sample and/or said carrier fluid such that said sample remains enveloped in said carrier fluid;
Claim 1: “passing the set of combined droplets through a plurality of thermal zones thereby allowing the target nucleic acid, if present, to be amplified in each droplet”.
and (d) analyzing said plurality of droplets while enveloped within said carrier fluid to determine a presence or absence of a target analyte in said sample.
Claim 1: “detecting the presence or absence of, and/or determining the amount of, the amplified target nucleic acid in the droplets within the set of combined droplets while in the flow”.
Regarding instant claims 23, 24:
further comprising subjecting said plurality of droplets to a thermal cycling stage to generate amplicons of said target analyte;
further comprising delivering said plurality of droplets to a thermal zone in which an amplification reaction of said target analyte is performed
Claim 1: “passing the set of combined droplets through a plurality of thermal zones thereby allowing the target nucleic acid, if present, to be amplified in each droplet”.
Regarding instant claims 26, 27, 31:
further comprising subjecting said plurality of droplets to a detection stage;
further comprising detecting a signal from one or more droplets of said plurality of droplets during said detection stage, said signal indicative of said presence or absence of said target analyte;
further comprising detecting said signal from said target analytes or amplicons thereof while flowing said plurality of droplets pass a detection device
Claim 1: “detecting the presence or absence of, and/or determining the amount of, the amplified target nucleic acid in the droplets within the set of combined droplets while in the flow”.
Regarding instant claim 32:
wherein said detection stage is after said thermal cycling stage
Per the ‘230 claims, the amplification takes place before the detection.
Regarding instant claims 33, 34:
wherein said target analyte comprises nucleic acids;
wherein said nucleic acids comprise DNA or RNA
Claim 23: “wherein the target nucleic acid is DNA”.
Claims 20-24, 26, 27, 31-35 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 7,622,076. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘076 claims describe a system for providing a plurality of sample droplets enveloped within a continuous flow of immiscible carrier fluid (specifically, silicone oil), subjecting the sample droplets to a thermal cycling stage for performing PCR, and an optical detection stage for analysis. PCR implies the analysis of DNA, a nucleic acid. The ‘076 claims moreover disclose a sample preparation stage comprising a centrifuge for separation of samples from an input fluid and for introduction of the samples to the primary carrier fluid.
Claims 20, 21, 23, 24, 26-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,676,786. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘786 claims describe a system for providing a plurality of sample droplets enveloped within a flow of immiscible carrier fluid (specifically, oil), subjecting the sample droplets to a thermal cycling stage for performing PCR, and an optical detection stage for analysis. PCR implies the analysis of DNA, a nucleic acid. The ‘786 claims moreover disclose a sample preparation stage comprising a centrifuge for separation of samples from an input fluid and for introduction of the samples to the primary carrier fluid.
Claims 20, 21, 23, 24, 26-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-19 of U.S. Patent No. 11,807,902. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘902 claims disclose a method for providing a plurality of sample droplets enveloped within a flow of immiscible carrier fluid (specifically, oil), subjecting the sample droplets to a thermal cycling stage for performing PCR, and an optical detection stage for analysis. The ‘902 claims moreover disclose separating nucleic acid strands from samples of an input fluid, and the analysis of rare mutated cells.
Conclusion
No claims are free of the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681