DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. 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.
Preliminary Amendment
3. The preliminary amendment filed 16 August 2023, in which claims 3, 5-6, 9, 11, 13-16, 19, 21, 23, 27, 30, and 32 were amended and claims 7-8, 10, 12, 17-18, 20, 22, 24-26, 28-29, 31, 33-34, 36-68, and 70-99 were canceled is acknowledged.
Election/Restrictions
4. Applicant’s election without traverse of Group I, Species 1b, and Species 2b in the reply filed on 8 April 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
However, the previous requirement for species election is withdrawn.
Claim 69 is therefore withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8 April 2026.
5. Claims 1-6, 9, 11, 13-16,19, 21, 23, 27, 30, 32, and 35 are under prosecution.
Information Disclosure Statement
6. The Information Disclosure Statement filed 16 August 2023 is acknowledged and has 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
7. The use of trade names or marks used in commerce (including but not necessarily limited to REXEED, 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.
Claim Interpretation
8. The claims are subject to the following interpretation:
A. Claim 2 is drawn to “semi-permeable hydrogel microcapsules.” Pages 16-17 of the instant specification explicitly states that “the term “semi-permeable hydrogel microcapsules” refers to hydrogel particles comprising dextran-rich cores and polyethylene glycol diacrylate (PEGDA)-rich shells.” Thus, the claimed “semi-permeable hydrogel microcapsules” as subject to the limiting definition described within the specification.
B. Claims 11 and 23 each recite different groups of limitations separated by semicolons, concluding with “or any combination thereof.” Thus, the claims only require at least one of the groups.
Claim Rejections - 35 USC § 112
9. 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.
10. Claims 2 and 35 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. As noted above, claim 2 is bound by the limiting definition of semi-permeable hydrogel microcapsules as “comprising dextran-rich cores and polyethylene glycol diacrylate (PEGDA)-rich shells.” The term “rich” in claim 2 is a relative term which renders the claim indefinite. The term “rich” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
B. Claim 35 is indefinite in the recitation “the random aliquots,” which lacks antecedent basis because there is no previous recitation of “random” aliquots.
Claim Rejections - 35 USC § 103
11. 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.
12. 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.
13. Claims 1, 6, 11, 14-15, 23, 27, 30 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Norberg et al. U.S. Patent Application Publication No. US 2020/0131502 A1, published 30 April 2020) and Arab et al. (U.S. Patent Application Publication No. US 2021/0053065 A1, published 25 February 2021).
Regarding claim 1, Norberg et al. teach methods wherein a biomolecule is encapsulated in a semi-permeable biomolecule in a microcapsule, in the form of hydrogel polymer bead, which retains the biomolecule but allows diffusion of regents through the bead (paragraph 0007); thus, the microcapsule is semi-permeable. Norberg et al. further teach the biomolecules include nucleic acids, in the form of genomic DNA or viral nucleic acids (paragraph 0051); thus, it would have been obvious to use viral genomes. Norberg et al. further teach the microcapsules are subjected to sequential assays including nucleic acid amplification and nucleic acid sequencing (paragraph 0007); thus, it would have been obvious to amplify the genomic material and sequence the amplified molecules. Norberg et al. also teach the methods have the added advantage of diagnosing infectious diseases (paragraph 0004). Thus, Norberg et al. teach the known techniques discussed above.
Norberg et al. teach a plurality of microcapsules (i.e., beads; paragraphs 0022-0225), and that a microcapsule includes a single cell (paragraph 0007), as well a single cell genome amplification (paragraph 0030). Thus, it would have been obvious to have the viral genome in a single microcapsule.
Norberg et al. do not explicitly teach aliquoting a sample.
However, Arab et al. teach methods wherein a liquid sample (paragraph 0054) is aliquoted into a plurality of microcapsules (i.e., droplets; paragraph 0007). Arab et al. also teach the sample comprises more than one species or microorganism (Abstract), that droplets having a single species (paragraphs 0006 and 0057), and that the methods have the added advantage allowing determination of the aliquoted sample to one or more test reagents (Abstract). Thus, Arab 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 the cited prior art. The combination would result in forming microcapsules each having a different single species from a mix of species therein as discussed by Arab et al., wherein each species comprises a viral genome as taught by Norberg et al., thereby arriving 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 allowing diagnosis of infectious diseases as explicitly taught by Norberg et al. (paragraph 0007) and allowing determination of the aliquoted sample to one or more test reagents as explicitly taught by Arab 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 with predictable results because the known techniques of the cited prior art predictably result in techniques useful for analyzing samples.
Regarding claim 6, the method of claim 1 is discussed above. Arab et al. teach the sample is a liquid biological sample, in the form of saliva (paragraph 0054).
The optional limtations are not required.
Regarding claim 11, the method of claim 1 is discussed above. Arab et al. teach diluting the sample (paragraph 0055), as well as each microcapsule (i.e., droplet) comprises one (i.e., as single) microorganism (i.e., as opposed to also including its progeny; paragraph 0057). Norberg et al. teach a single microcapsule (i.e., bead) encapsulates a single DNA molecule (paragraph 0032) using dilution (paragraph 0059). Thus, it would have been obvious to dilute the sample so that only one genomic molecule is encapsulated in each microcapsule.
Regarding claim 14, the method od claim 1 is discussed above. Norberg et al. teach the samples are cells (i.e., rather than isolated DNA; paragraphs 0119-0120 and 0122). Arab et al. teach non-sterile samples including urine or skin (paragraph 0054); thus, it would have been obvious to have a raw sample.
In addition, 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 Arab et al. that the sample can be processed in preparation for analysis (paragraph 0055) encompasses the alternate embodiment wherein the sample is not processed, and thus is “raw.”
Regarding claim 15, the method of claim 1 is discussed above. Arab et al. teach solid samples (e.g., soft tissue; paragraph 0054), and that the sample is an aqueous liquid that is filtered and that the microcapsules (i.e., droplets) are formed from a liquid. Thus, it would have been obvious that a solid sample could be dispersed into a liquid sample.
The optional limtations are not required.
Regarding claim 23, the method of claim 1 is discussed above. Arab et al. teach filtering the sample (paragraph 0055).
Regarding claim 27, the method of claim 1 is discussed above. Norbert et al. teach the microcapsules (i.e., beads) are distributed to wells of microplate and lysed (paragraph 0112), which would necessarily occur prior to sequencing.
Whle the lysis step is taught by Norbert et al., it is noted that this is an optional limtations that is not required.
Regarding claim 30, the method of claim 1 is discussed above. Norberg et al. teach barcoding amplfied genetic elments prior to sequecning; namely, the amplification primers include barcodes (paragraph 0076), which get added during amplification and prior to sequencing.
The optional limtations are not required.
In addition, with respect to the order of steps in claims 27 and 30, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
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, counsel’s mere arguments cannot take the place of evidence in the record.
Regarding claim 32, the method of claim 1 is discussed above. Norberg et al. teach genomic DNA and viral nucleic acids (paragraph 0051), a plurality of microcapsules (i.e., beads; paragraphs 0022-0225), and that a microcapsule includes a single cell (paragraph 0007), as well a single cell genome amplification (paragraph 0030). Thus, it would have been obvious to have the viral genomic DNA in a single microcapsule.
Arab et al. teach the sample comprises more than one species or microorganism (Abstract) and that droplets having a single species (paragraphs 0006 and 0057). Thus, the combination would result in forming microcapsules each having a different single species from a mix of species therein as discussed by Arab et al., wherein each species comprises a viral genome as taught by Norberg et al., thereby arriving at the claimed plurality of DNA viral genomes.
14. Claims 2, 5 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Norberg et al. U.S. Patent Application Publication No. US 2020/0131502 A1, published 30 April 2020) and Arab et al. (U.S. Patent Application Publication No. US 2021/0053065 A1, published 25 February 2021) as applied to claim 1 above, and further in combination with Mazutis et al. (U.S. Patent Application Publication No. US 2020/0400538 A1, published 24 December 2020).
It is noted that while claim 23 is rejected as described above, the claim is also obvious using the interpretation outlined below.
Regarding claims 2, 5 and 23, the method of claim 1 is discussed in Section 13.
While Norberg et al. teach microcapsules (i.e., beads) having core-shell structures (e.g., paragraph 0024), the previously cited prior art does not teach the dextran-rich core PEGDA-rich shell particles (i.e., claim 2).
However, Mazutis et al. teach methods comprising forming a plurality of capsules (claim 11 of Mazutis et al.), wherein nucleic acid molecules are encapsulated in the semi-permeable microcapsules (paragraph 0001). The microcapsules comprise dextran-rich cores and PEG-rich shells (i.e., claim 2; paragraph 0009), and have volumes of 1-100 pl (i.e., claim 5; paragraph 0127). Mazutis et al. also teach DNAse treatment prior to PCR amplification (i.e., claim 23; paragraph 0072), and that the methods have the added advantage of allowing dissolution at a selected step in order to release the encapsulated species (Abstract). Thus, Mazutis et al. teach the known techniques discussed above.
It is 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 also 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.
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 Mazutis et al. with the previously cited prior art 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 advantage of allowing dissolution at a selected step in order to release the encapsulated species as explicitly taught by Mazutis et al. (Abstract). In addition, it would have been obvious to the ordinary artisan that the known techniques of Mazutis et al. could have been combined with the previously cited prior art with predictable results because the known techniques of Mazutis et al. predictably result in microcapsules useful for analyzing samples.
15. Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Norberg et al. U.S. Patent Application Publication No. US 2020/0131502 A1, published 30 April 2020) and Arab et al. (U.S. Patent Application Publication No. US 2021/0053065 A1, published 25 February 2021) as applied to claim 1 above, and further in combination with Fathollahi et al. (U.S. Patent Application Publication No. US 2018/0067038 A1, published 8 March 2018).
Regarding claims 3-4, the method of claim 1 is discussed above in Section 13.
While Arab et al. teach removal of droplets and disposing them on a plate for further analysis (paragraph 0086), and while Norberg et al. teach placement of the microcapsules in wells of a plate (paragraph 0112), the previously cited prior art does not teach separating aliquots containing amplified genomic material.
However, Fathollahi et al. teach methods wherein aliquots (i.e., droplets) comprising amplified nucleic acids are isolated (i.e., claim 3) and the placement of amplified aliquots in a microwell (i.e., claim 4; paragraph 0037). Fathollahi et al. further teach the collection of the droplets for downstream sequencing in another well, which has the added advantage of allowing next-generation sequencing (paragraph 0095). Thus, Fathollahi et al. teach the known techniques discussed above.
It is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed order of steps is an obvious variant of the steps 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 Fathollahi et al. with the previously cited prior art 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 advantage of allowing next generation sequencing as explicitly taught by Fathollahi et al. (paragraph 0095). In addition, it would have been obvious to the ordinary artisan that the known techniques of Fathollahi et al. could have been combined with the previously cited prior art with predictable results because the known techniques of Fathollahi et al. predictably result in techniques useful for sequencing nucleic acids.
16. Claims 9, 15-16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Norberg et al. U.S. Patent Application Publication No. US 2020/0131502 A1, published 30 April 2020) and Arab et al. (U.S. Patent Application Publication No. US 2021/0053065 A1, published 25 February 2021) as applied to claim 1 above, and further in combination with Rublee et al. (U.S. Patent Application Publication No. US 2012/0021429 A1, published 26 January 2012).
It is noted that while claim 15 is rejected as described above, the claim is also obvious using the interpretation outlined below.
Regarding claims 9, 15-16, and 19, the method of claim 1 is discussed above in Section 13.
Arab et al. teach solid samples (e.g., soft tissue; paragraph 0054), and that the sample is an aqueous liquid that is filtered and that the microcapsules (i.e., droplets) are formed from a liquid. Thus, it would have been obvious that a solid sample could be dispersed into a liquid sample (i.e., claim 15).
The previously cited prior art does not teach lake water samples(i.e., claim 9) or solid sample., claims 15-16 and 19).
However, Rublee et al teach methods wherein environmental samples, in the form of lake seawater (i.e., coastal; (paragraph 0006), and river samples (i.e., claim 9; paragraph 0091) are monitored, including using genomic DNA from water samples for PCR analysis (paragraph 0093). Rublee et al. alternatively teach solid samples (i.e., claims 15-16), in the form of soil samples (i.e., claim 19; paragraph 0044), and that the methods have the added advantage of allowing monitoring of physical or biological characteristics of ecosystems (paragraph 0043).
The optional limtations are not required.
Thus, Rublee 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 Rublee et al. with the previously cited prior art 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 advantage of allowing monitoring of physical or biological characteristics of ecosystems as explicitly taught by Rublee et al. (paragraph 0043). In addition, it would have been obvious to the ordinary artisan that the known techniques of Rublee et al. could have been combined with the previously cited prior art with predictable results because the known techniques of Rublee et al. predictably result in samples useful for monitoring ecosystems.
17. Claims 13 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Norberg et al. U.S. Patent Application Publication No. US 2020/0131502 A1, published 30 April 2020) and Arab et al. (U.S. Patent Application Publication No. US 2021/0053065 A1, published 25 February 2021) as applied to claim 1 above, and further in combination with Taft et al. (U.S. Patent Application Publication No. US 2008/0269549 A1, published 30 October 2008).
It is noted that while claim 15 is rejected as described above, the claim is also obvious using the interpretation outlined below.
Regarding claims 13 and 15, the method of claim 1 is discussed above in Section 13.
Arab et al. teach solid samples (e.g., soft tissue; paragraph 0054), and that the sample is an aqueous liquid that is filtered and that the microcapsules (i.e., droplets) are formed from a liquid. Thus, it would have been obvious that a solid sample could be dispersed into a liquid sample (i.e., claim 15).
None of the previously cited prior art teach cryopreservation.
However, Taft et al. teach methods wherein microcapsules (i.e., droplets) are cryopreserved (paragraph 0012) and thawed (paragraph 0044), which has the added advantage of allowing control of the volume and number of aliquots (Abstract). Thus, Taft et al. teach the known techniques discussed above.
It is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed order of steps is an obvious variant of the steps 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 Taft et al. with the previously cited prior art 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 advantage of allowing control over the volume and number of aliquots as explicitly taught by Taft et al. (Abstract). In addition, it would have been obvious to the ordinary artisan that the known techniques of Taft et al. could have been combined with the previously cited prior art with predictable results because the known techniques of Taft et al. predictably result in useful techniques for storing sample prior to use.
18. Claims 16 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Norberg et al. U.S. Patent Application Publication No. US 2020/0131502 A1, published 30 April 2020), Arab et al. (U.S. Patent Application Publication No. US 2021/0053065 A1, published 25 February 2021), and Taft et al. (U.S. Patent Application Publication No. US 2008/0269549 A1, published 30 October 2008). as applied to claim 15 above, and further in combination with Rublee et al. (U.S. Patent Application Publication No. US 2012/0021429 A1, published 26 January 2012) based on the citations and rationale provided above.
19. Claims 11 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Norberg et al. U.S. Patent Application Publication No. US 2020/0131502 A1, published 30 April 2020) and Arab et al. (U.S. Patent Application Publication No. US 2021/0053065 A1, published 25 February 2021) as applied to claim 1 above, and further in combination with Meersseman et al. (U.S. Patent Application Publication No. US 2018/0291367 A1, published 11 October 2018).
It is noted that while claim 11 is rejected as described above, the claim is also obvious using the interpretation outlined below.
Regarding claims 11 and 21, the method of claim 1 is discussed above in Section 13.
None of the previously cited prior art teaches enriching for extracellular genetic elements.
However, Meersseman et al. teach methods wherein extracellular viral nucleic acids are isolated (paragraph 0008), and that the extracellular nucleic acids are of interest in surveillance of disease progression (paragraph 0033). Thus, Meersseman et al. teach the known techniques discussed above.
It is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed order of steps is an obvious variant of the steps 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 Meersseman et al. with the previously cited prior art 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 advantage of allowing providing a sample of interest in the surveillance of disease progression as explicitly taught by Meersseman et al. (paragraph 0033). In addition, it would have been obvious to the ordinary artisan that the known techniques of Meersseman et al. could have been combined with the previously cited prior art with predictable results because the known techniques of Meersseman et al. predictably result in useful samples for disease monitoring.
20. Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Norberg et al. U.S. Patent Application Publication No. US 2020/0131502 A1, published 30 April 2020), Chiu et al. (U.S. Patent Application No. US 2021/0087618 A1, published 25 March 2021) and Ismagilov et al. (U.S. Patent Application Publication No. US 2012/0028342 A1, published 2 February 2012).
Regarding claim 35, Norberg et al. teach methods wherein a biomolecule is encapsulated in a semi-permeable biomolecule in a microcapsule, in the form of hydrogel polymer bead, which retains the biomolecule but allows diffusion of regents through the bead (paragraph 0007); thus, the microcapsule is semi-permeable. Norberg et al. further teach the biomolecules include nucleic acids, in the form of genomic DNA or viral nucleic acids (paragraph 0051); thus, it would have been obvious to use viral genomes. Norberg et al. further teach the microcapsules are subjected to sequential assays including nucleic acid amplification and nucleic acid sequencing (paragraph 0007); thus, it would have been obvious to amplify the genomic material and sequence the amplified molecules. Norberg et al. also teach the methods have the added advantage of diagnosing infectious diseases (paragraph 0004). Thus, Norberg et al. teach the known techniques discussed above.
Norberg et al. do not teach random aliquots.
However, Chiu et al. teach methods of performing nucleic acid amplification in droplets (Abstract), wherein the droplets are randomly distributed (paragraph 0181). Chiu et al. also teach detection of viral load based on amplification (paragraph 0050), and that the amplification quantifies the absolute number of viral genomes (i.e., template copies) and accurately calculates the concentration (paragraph 0050); thus, because the concentration and number of copies is known, the volume must also be known. Chiu et al. also teach the methods have the added advantage of providing an important data point for determining the amend of therapeutic drugs given to a patient (paragraph 0050). Thus, Chiu et al. teach the known techniques discussed above.
In addition, Ismagilov et al. teach methods wherein nucleic acid amplification is performed in droplets (paragraph 0407) and quantitation of viral load (paragraph 0382). Ismagilov et al. further teach the volume is known (paragraph 0376), and that the methods have the added advantage of allowing monitoring antiretroviral therapy (paragraph 0416). Thus, Ismagilov 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 the cited prior art 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:
Allowing providing a sample of interest in the diagnosing infectious diseases as explicitly taught by Norberg et al. (paragraph 0004);
Providing an important data point for determining the amend of therapeutic drugs given to a patient as explicitly taught by Chiu et al. (paragraph 0050); and
Allowing monitoring antiretroviral therapy as explicitly taught by Ismagilov et al. (paragraph 0416).
In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art cold have been combined with predictable results because the known techniques of cited prior art predictably result in useful techniques for analyzing patient samples.
Conclusion
22. No claim is allowed.
23. 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
Prosecution Insights