DETAILED ACTION
Notice of Pre-AIA or AIA Status and New Examiner
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Please note that the examiner for this application has changed. Please address future correspondence to Robert T. Crow (Art Unit 1683) whose telephone number is (571) 272-1113.
Election/Restrictions and Status of the Claims
2. The previous species election is withdrawn.
Claims 1-20 are under prosecution.
Information Disclosure Statement
3. The Information Disclosure Statements filed 20 April 2023 and 15 November 2023 are acknowledged and have been considered.
It is noted that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification and Drawings
4. The use of trade names or marks used in commerce (including but not necessarily limited to Cy3 and Cy5), has been noted in this application. Any trade names or marks should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
5. Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by:
I. The appropriate fee set forth in 37 CFR 1.17(h);
II. One set of color drawings or color photographs, as appropriate, if submitted via EFS-Web or three sets of color drawings or color photographs, as appropriate, if not submitted via EFS-Web; and, unless already present,
III. An amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
6. A statement from Applicant that there is no intention to have color drawings will result in acceptance of the drawings; otherwise, the conditions set forth above must be met in order for the color drawings to be accepted.
Claim Objections
7. Applicant is advised that should claim 15 be found allowable, claim 16 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 4-6, 9, and 12 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.
A. Claim 4 is indefinite in the recitation “at least about.” The phrase “at least” typically indicates a minimum point; however, the phrase “at least” is controverted by the term “about,” which implies that values above and below the indicated amount are permitted. Therefore, the juxtaposition of these two terms makes it unclear what minimum values are encompassed by the claim.
In Amgen, Inc. v. Chugai Pharmaceutical co., 927 F.2d 1200 (CAFC 1991), the CAFC stated, “[t]he district court held claims 4 and 6 of the patent invalid because their specific activity of “at least about 160,000” was indefinite.” After review, the CAFC states “[w]e therefore affirm the district court’s determination on this issue.” Thus, the CAFC found the phrase “at least about” indefinite where the metes and bounds of the term were not defined in the specification. See MPEP 2173.05(b) III.
B. Claim 5 is indefinite because while it is drawn to primer, it recites specific species of pathogens. For the purposes of examination, the claim is interpreted as requiring primers for the listed pathogens.
In addition, it is unclear if the “5’” listed in claim 5 refers only to 6-FAM.
Further, as claim 5 does not use standard Markush language, it is unclear if the “and/or” in the last line of the claim indicates that the “or” option refers only to CMV, thus requiring all of the previous entries “or” CMV, or if “or” means that any one of the listed species are alternatives.
For the purposes of examination, the word “or” is interpreted meaning any one of the listed species must be present.
C. Claim 6 contains the trademarks/trade names CY5 and CY3. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a brand name and, accordingly, the identification/description is indefinite.
Further, as claim 6 does not use standard Markush language, it is unclear if the “and/or” in the last line of the claim indicates that the “or” option refers only to TAMRA, thus requiring all of the previous entries “or” TAMRA, or if “or” means that any one of the listed species are alternatives.
For the purposes of examination, the word “or” is interpreted meaning any one of the listed species must be present.
D. Claim 9 is indefinite in the recitation “the chamber depth is between 50% and 200%,” as it is unclear how droplets in the droplet generation channel can fit into a chamber whose depth is smaller than the generator channel itself.
E. Claim 12 is indefinite in the recitation “the optical detection unit,” which lacks antecedent basis because claim 1 does not recite an optical detection unit.
Claim Rejections - 35 USC § 103
10. 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.
11. 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.
12. Claims 1-9, 12-14 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Colston et al. (U.S. Patent Application Publication No. US 2010/0173394 A1, published 8 July 2010) in combination with Abram et al. (Lab Chip, vol. 3, pages 477-489 and Supplementary Materials, published 2019).
Regarding claim 1, Colston et al. teach methods of detecting infections agents in blood samples (paragraph 0157), including pathogens (paragraph 1142). comprising loading the sample in a well (paragraph 0200) combining the sample with reagents including primer pairs, probes, and a buffer (paragraph 0159), wherein the probes are labeled (paragraph 0178), the sample and reagents are mixed in the well (paragraph 0286), and wherein dPCR (i.e., digital PCR) is performed (paragraph 0139). Colston et al. further teach droplet generator channel (e.g., aperture 2310; Figure 59 and paragraph 0644), performing the PCR in a chamber, in the form of a PCR channel (paragraph 0146), wherein the channels are microfluidic (paragraph 0183). Colston et al. also teach the sample well (i.e., chamber) is fluidically connected to the droplet generation channel (paragraph 0593), detection of fluorescence based on the presence of a target (paragraph 0098), and that the methods have the added advantage of reduced background and assay time (paragraph 0138). Thus, Colston et al. teach the known techniques discussed above.
Colston et al. do not explicitly tach the entire device is a microfluidic device.
However, Abram et al. teach methods utilizing microfluidic devices (“Introduction”), wherein the sample inlet is fluidically connected to droplet generation channels (Figure 2), the samples are blood samples from patients (“Introduction”), and that the methods have the added advantage of unprecedented high sensitivity (Abstract). Thus, Abram et al. teach the known techniques discussed above.
In addition, it is noted that the courts have held that the rearrangement of parts within a device is obvious when the arrangement does not specifically modify the operation of the device (In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950)). See MPEP §2144.04. Thus, any arrangement of fluidic connections is obvious.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the cited prior art to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantages of reduced background and assay times as explicitly taught by Colston et al. (paragraph 0138) and unprecedented high sensitivity as explicitly taught by Abram et al. (Abstract). In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined l with predictable results because the known techniques of the cited prior art predictably result in methods and devices useful for detecting pathogens.
Regarding claims 2-3, the method of claim 1 is discussed above. Abram et al. teach the infection is sepsis arising from pathogens (Abstract).
Regarding claim 4, the method of claim 3 is discussed above. Abram et al. teach that the pathogens are present at about 10 CFU/mL (Abstract).
It is also noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have further found that “where 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). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
Regarding claim 5, the method of claim 1 is discussed above.
It is noted that the group listed in claim 5 recites “and/or” before the last alternative. Thus, when the term “or” is applied, the claim only requires one of the listed alternatives.
Colston et al. teach detection of S. aureus, EBV and CMV (paragraph 1141-1142). Abram et al. teach detection of E. coli (“Expansive detection of resistance…”).
Regarding claim 6, the method of claim 1 is discussed above. Abram et al. teach probes having 6-FAM at the 5’ end (Supplementary Materials, Table S1).
In addition, it is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
In the instant case, the FAM taught by Colston et al. (paragraph 1092) is believed to be the 6-FAM of the instant claim.
Alternatively, the courts have stated:
[c]ompounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious) (see MPEP 2144.09).
Therefore, the claimed positioning of the carboxy group at the 6 position of FAM is an obvious variation over the prior art.
Further, with respect to Colston et al, the positioning of the FAM at the 5’ end is an obvious variant over the prior art, in particular since Colston et al. teach reporter quencher labels as part of a molecular beacon are at the 5’ end of a probe-primer pair (paragraph 0178).
Regarding claim 7, the method of claim 1 is discussed above. Colston et al. teach a well (paragraph 0200); which is part of an array of wells (paragraph 0196): thus there is at least two wells since there is an array of wells.
Regarding claim 8, the method of claim 1 is discussed above in Section 12.
It is noted that the open claim language “comprising” found in the instant claim encompasses more than 16 targets being detected by mor than four primer mixes and probes in each well.
Colston et al. teach multiplexed assays wherein multiple targets are detected via amplification within the same droplet (paragraphs 0165 and 0211), as well as 50 pairs of primers each for specific gene sequences in each droplet (paragraph 1147) and multiple on-color target specific probes (paragraph 1154). Thus, it would have been obvious to detect at least 16 sepsis targets by having at least 4 specific primer sets and at least 4 color-specific prober in each sample well.
Colston et al. further teach each droplet generator has a sample well attached thereto (paragraph 0286), as well as at least four droplet generators (Figure 27 and paragraph 0294-0295).
Regarding claim 9, the method of claim 1 is discussed above. Colston et al. teach the droplet generator widens to a chamber so that the droplets form a monolayer based on the diameter of the droplets (paragraph 0297; see also Fig. 57). Thus, it would have been obvious to have a chamber depth slightly larger than the droplet generator dimensions in order to forma monolayer.
Alternatively, it is noted that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments (see MPEP § 2123). Thus, the teaching of Colston et al. that the generator channel may be widen (paragraph 0297) encompasses the alternate embodiment wherein the generator channel is not wider, and thus is 100% the depth.
In addition, it is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists, and that where 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.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
Regarding claim 12, the method of claim 1 is discussed above. Colston et al. teach a controller that determines the percentage of droplets having a positive (i.e., higher) amplification signal (paragraph 0450) , which necessarily included the calculation of the lower (i.e., negative) signals, both of which are counted and analyzed (paragraph 0587). Colston et al also teach the droplets are imaged (paragraph 0311), and detected based on size (paragraph 0387), and that the controller is used with a memory device that carries information about processing performed (paragraph 0193). Colston et al also each software (paragraph 1034); thus it would have been obvious to have software for performing the claimed functions.
It is also noted that the claim does not actually require the limitations to be performed as active method steps.
Regarding claim 13, the method of claim 1 is discussed above. Colston et al. teach a pressure manifold for generating droplets (paragraph 0287).
Regarding claim 14, the method of claim 1 is discussed above. Colston et al teach a thermocycling apparatus for performing nucleic acid amplification (i.e., PCR) in the chamber (paragraph 0187 and Figure 3A).
Regarding claim 18, the method of claim 1 is discussed above. Colston et al. teach he PCR chamber is a PCR channel (paragraph 0146), and that the channels have depths of 100 microns (paragraph 0585).
Regarding claim 19, the method of claim 1 is discussed above. Colson et al. teach the droplet channel dimensions are each independently 5 to 350 microns (paragraph 0690).
In addition, with respect to claims 18-19, it is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists, and that where 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.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
Regarding claim 20, the method of claim 1 is discussed above. Colston et al. teach (single) chamber 1326 connected to droplet generation channel 1322 (Figure 31 and paragraph 0303).
13. Claims 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Colston et al. (U.S. Patent Application Publication No. US 2010/0173394 A1, published 8 July 2010) in combination with Abram et al. (Lab Chip, vol. 3, pages 477-489 and Supplementary Materials, published 2019) as applied to claim 1 above, and further in view of Bennet et al. (U.S. Patent Application Publication No. US 2012/0200700 A1, published August 2012).
Regarding claim 10, the method of claim 1 is discussed above in Section 12. Colston et al teach an optical detection unit, in the form of an imaging system having alight emission generator (i.e., a laser), and an optical detector to detect fluorescent light (i.e., a CCD camera; paragraph 0307), as well as detection of reflected light (paragraph 0839). The optical system further measures intensity and wavelength of the florescent light (paragraph 0114), and the collection of image data (paragraphs 0300a and 0914), as well as memory circuitry (i.e., a hard drive; paragraph 0214). Thus, because the image data is collected, it is stored. Colston et al further teach the optical detector (i.e., camera) is supported by an XYZ stage (paragraph 0307), and that well plates supported by a XYZ stage (paragraph 247).
Neither Colston et al. nor Abram et al. teach the optical detection unit is integrated with the stage.
However, Bennett et al. teach integrated optical detection systems comprising lasers, cameras, and processors on a platform (paragraph 0032), and that integration into a platform allows for educed overall size and consolidated costs (paragraph 0002). Thus, Bennett et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Bennett et al. with the teachings of the cited prior art to integrate the XYZ platform and optics into a single platform to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of allowing reduced overall size and consolidated costs as explicitly taught by Bennett et al. (paragraph 0002). In addition, it would also have been obvious to the ordinary artisan that the known techniques of Bennett et al. could have been applied to the cited prior art with predictable results because the known techniques of Bennett et al. predictably result in useful arrangements of components associated with optical detection.
It is also noted that the claim does not actually require the limitations to be performed as active method steps.
Regarding claim 11, the method of claim 10 is discussed above. Colston et al. teach the light signal is detected and higher and lower (i.e., positive and negative) signals are counted and analyzed (paragraph 0587), that the droplets are imaged (paragraph 0311), and detected based on size (paragraph 0387). Colston et al. further each these signals are compared to a threshold (paragraph 1031), as well as an optical reading control unit, in the form of an analyzer which processes the detection data (paragraph 0321).
It is also noted that the claim does not actually require the limitations to be performed as active method steps.
14. Claims 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Colston et al. (U.S. Patent Application Publication No. US 2010/0173394 A1, published 8 July 2010) in combination with Abram et al. (Lab Chip, vol. 3, pages 477-489 and Supplementary Materials, published 2019) as applied to claim 1 above, and further in view of Liu et al. (U.S. Patent No. US 9,910,012 0700 B2, issued 6 March 2018).
Regarding claims 15-16, the method of claim 1 is discussed above in Section 12.
Neither Colston et al. nor Abram et al. teach the claimed hydrodynamic resistance.
However, Liu et al. teach methods utilizing microfluidic devices (Abstract), wherein the channels have hydrodynamic resistance that is about 1000 times higher than the chamber, which has the added advantage of enabling the coordinated movement of small amounts of material through the device (column 4, lines 1-15). Thus, Liu et al. teach the known techniques discussed above.
It is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists, and that where 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.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Liu et al. with the teachings of the cited prior art to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of enabling the coordinated movement of small amounts of material through the device as explicitly taught by Liu et al. (column 4, lines 1-15). In addition, it would also have been obvious to the ordinary artisan that the known techniques of Liu et al. could have been applied to the cited prior art with predictable results because the known techniques of Liu et al. predictably result in channel and chamber dimension volumes useful for moving fluids.
15. Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Colston et al. (U.S. Patent Application Publication No. US 2010/0173394 A1, published 8 July 2010) in combination with Abram et al. (Lab Chip, vol. 3, pages 477-489, published 2019) as applied to claim 1, and further in combination with Ching et al.(U.S. Patent Application Publication No. US 2012/0288897 A1, published 15 November 2012).
Regarding claim 17, the method of claim 1 is discussed above in Section 12.
Neither Colston et al. nor Abram et al. teach the claimed volumes.
However, Ching et al. teach dPCR chambers having volumes of 20 microliters, which has the added advantage of allowing either single or multiple targets to be analyzed in a chamber (paragraph 0507). Thus, Ching et al. teach the known techniques discussed above.
It is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists, and that where 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.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Ching et al. with the teachings of the cited prior art to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of allowing either single or multiple targets to be detected in a chamber as explicitly taught by Ching et al. (paragraph 0507). In addition, it would also have been obvious to the ordinary artisan that the known techniques of Ching et al. could have been applied to the cited prior art with predictable results because the known techniques of Ching et al. predictably result in chamber volumes useful in digital PCR assays.
16. It is noted that while claims 1-20 have been rejected as described above, the claims are also obvious using the interpretation outlined below.
19. Claims 1-7 and 9-20 are rejected under 35 U.S.C. 103 as being unpatentable over LI et al. (PCT International Patent Application Publication No. WO 2020/0102702 A1, published 22 May 2000) in combination with Abram et al. (Lab Chip, vol. 3, pages 477-489 and Supplementary Materials, published 2019).
Regarding claims 1-7 and 9-20, Li et al. teach all of the structural limitations of the claims microfluidic device (e.g., generally following the numerical order of claims 1 and 9-20: paragraphs 0010-0011; 0015; 0036; 0012; 0035; and 0013), and at least one well (paragraph 0010), which encompasses two wells (i.e., claim 7). and that the device is used for digital PCR (paragraph 0005) and has the added advantage of avoiding undesirable post-PCR contamination (paragraph 0009). Thus, Li et al. teach the known techniques discussed above.
Li et al. do not teach the method steps of claim 1 or the limitations of claims 2-6.
However, Abram et al. teach methods utilizing microfluidic devices (“Introduction”), wherein the sample inlet is fluidically connected to droplet generation channels (Figure 2), the samples are blood samples from patients (i.e., claim 1; “Introduction”). Abram et al. also teach pathogenic primer mixes, labels probes, and buffers for dPCR, and detection of amplification in the droplets (Supplementary Materials).
Abram et al. also tech the limitations of claims 2-6 as discussed above, and that the methods have the added advantage of unprecedented high sensitivity (Abstract). Thus, Abram et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Li et al. with the teachings of the Abram et al. to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantages of avoiding undesirable post-PCR contamination as explicitly taught by Li et al. (paragraph 0009) and unprecedented high sensitivity as explicitly taught by Abram et al. (Abstract). In addition, it would also have been obvious to the ordinary artisan that the known techniques the cited prior art could have been combined with predictable results because the known techniques of the cited prior art. predictably result in devices and steps useful in digital PCR assays.
20. Claims 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over LI et al. (PCT International Patent Application Publication No. WO 2020/0102702 A1, published 22 May 2000) in combination with Abram et al. (Lab Chip, vol. 3, pages 477-489, published 2019) as applied to claim 1 above, and further in view of Colston et al. (U.S. Patent Application Publication No. US 2010/0173394 A1, published 8 July 2010).
It is noted that while claims 5-6 have been rejected as described above, the claims are also obvious using the interpretation outlined below.
Regarding claims 5-8, the method of claim 1 is discussed above in Section 19.
While neither Li et al. nor Abram et al. teach the limitations of claims 7-8, Colston et al teach these limitations, as well as those of claim 5-6, as discussed above, and that the methods have the added advantage of reduced background and assay times (paragraph 0138). Thus, Colston et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined Colston et al. with the cited prior art to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantages of reduced background and assay times as explicitly taught by Colston et al. (paragraph 0138). In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with Colston et al. predictable results because the known techniques of the Colston et al. predictably result in methods and devices useful for detecting pathogens.
Double Patenting
21. 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.
22. Claims 1-5 and 9-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,273,444 in view of Abram et al. (Lab Chip, vol. 3, pages 477-489, published 2019).
Both sets of clams are drawn to method using the same microfluidic devices, droplet generation, thermal cycling, etc. Any additional limitations of the ‘444 claims are encompassed by the open clam language “comprising: found in the instant claims.
The ‘444 claims do not teach dPCR amplification or the method steps of claims 2-6.
However, Abrahm et al. teach these limitations, and the rationale for combining, as discussed above. Thus, the claims are obvious over the ‘444 claims in view of the citations and rationale discussed above.
23. Claims 5-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,273,444 in view of Abram et al. (Lab Chip, vol. 3, pages 477-489, published 2019) as applied to claim 1 above, and further in view of Colston et al. (U.S. Patent Application Publication No. US 2010/0173394 A1, published 8 July 2010).
It is noted that while claims 5-6 have been rejected as described above, the claims are also obvious using the interpretation outlined below.
Regarding claims 5-8, the method of claim 1 is discussed above in Section 22.
Neither Abram et al. nor the ‘444 claims teach the limitations of claims 7-8.
However, Colston et al teach these limitations, as well as those of claim 5-6, as discussed above, as well as the rationale for combining as also discussed above.
Thus, the claims are obvious over the ‘444 claims in view of the citations and rationale discussed above.
Conclusion
24. No claim is allowed.
25. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert T. Crow whose telephone number is (571)272-1113. The examiner can normally be reached M-F 8:00-4:30.
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Robert T. Crow
Primary Examiner
Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683