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 .
MAINTAINED REJECTION
2. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon or correlation without significantly more. The claims recite a natural correlation between expression level of a composite biomarker and whether a subject has an infection. This judicial exception is not integrated into a practical application because data gathering steps required to use the correlation do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the physical steps of loading a sample into a fluidic device, performing processes within the device comprising extracting target nucleic acids using beads and removing said target nucleic acids from the beads and after such extraction amplifying the target nucleic acids, and measuring an expression level of a composite biomarker using the fluidic device were routine and conventional in the prior art, as indicated by Hodko et al. (US 2022/0307079), see paragraphs 0008-0019, 0029-0030, 0052, 0138, 0141, 0172, 0183, 0186, 0193-0195, 0198, and 0258-0259, and Briscoe et al. (US 2003/0129646), see paragraph 0024.
REPLY TO ARGUMENTS
3. With respect to the above rejection, the arguments of the response filed 05/14/26 on pages 14-16 have been fully considered, but are not found persuasive. The response argues that the claimed invention improves another technology or technical field in that it ‘provides an improved, rapid method for diagnosing a subject which may result in faster time-to-treatment of the subject.’ This is not found convincing because the pending claims are drawn to a prognostic correlation between infection in a subject and expression level of a composite biomarker, and the current guidelines do not mention improvements to diagnostic correlations, which are judicial exceptions. The claimed methods do not require any improvement in, for example, the technology or technical field of diagnosis or prognosis, involving, for example, an improved way of obtaining a sample from a patient or an improved way of extracting or amplifying nucleic acids. Thus, the rejection is maintained.
NEW GROUNDS OF REJECTION NECESSITATED BY THE AMENDMENT
4. 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.
5. 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.
6. Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable under Hodko et al. (US 2022/0307079) in view of Briscoe et al. (US 2003/0129646).
Regarding independent claim 1, Hodko discloses a method comprising: loading a blood sample into a fluidic device; performing nucleic acid related processes within the device using beads, including extracting and amplifying target nucleic acids, and measuring expression of a composite biomarker, and outputting whether a subject has or does not have an infection, within 60 minutes. See paragraphs 0008-0019, 0029-0030, 0052, 0138, 0141, 0172, 0183, 0186, 0193-0195, 0198, and 0258-0259.
Hodko does not disclose removing target nucleic acids from beads prior to amplifying them; rather, Hodko discloses amplifying them on the beads.
Regarding claim 2, Hodko discloses methods which omit the use of DNase and omit performing amplification of genomic DNA (RNA-based detection is disclosed in paragraph 0186).
Briscoe discloses, in the context of nucleic acid analysis within a microfluidic device, removing extracted nucleic acids from beads before amplifying them in solution in another chamber or compartment. See paragraph 0024.
One of ordinary skill in the art would have been motivated to modify the method of Hodko by first removing target nucleic acids from beads and then amplifying them in solution because Briscoe disclosed that like solid-phase amplification on beads, elution of nucleic acids from beads and amplifying them in solution was conventional in nucleic acid analysis in fluidic devices. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
7. Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe, and further in view of Wille et al. (US 2006/0281092).
The teachings of Hodko and Briscoe are discussed above.
Hodko and Briscoe do not disclose use of an RNA stabilization solution.
Wille discloses use of an RNA stabilization solution. See paragraph 0017.
One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe by using an RNA stabilization solution because Wille disclosed the advantage of using such a solution in RNA analysis. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
8. Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe, and further in view of Bommarito et al. (US 2011/0097814).
The teachings of Hodko and Briscoe are discussed above.
Hodko and Briscoe do not disclose preparing reagents by convection drying.
Bommarito discloses preparing reagents by convection drying for use in devices. See paragraphs 0116-0117.
One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe by preparing dried reagents using convection drying because Bommarito disclosed the advantage of using dried reagents prepared by convection drying. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
9. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe, and further in view of Zenhausern et al. (US 2010/0213063).
The teachings of Hodko and Briscoe are discussed above.
Hodko and Briscoe do not disclose use of bubble mixing.
Zenhausern discloses use of bubble mixing to facilitate binding of nucleic acids to beads. See paragraph 0227.
One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe by using bubble mixing because Zenhausern disclosed the use of bubble mixing to facilitate binding of nucleic acids to beads within a fluidic device. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
10. Claims 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe.
The teachings of Hodko and Briscoe are discussed above.
Hodko and Briscoe do not disclose an exact volume of blood sample such as less than 500 microliters (claim 6), nor the use of the set of informative genes required in claim 7.
One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe by using a blood sample volume of less than 500 microliters, and using the gene biomarker panel as recited in claim 7, because these would have merely involved routine optimization of known-important reaction parameters, which as well settled in U.S. patent practice does not support unobviousness (M.P.E.P 2144.05). In other words, the skilled artisan would have routinely optimized the blood sample volume and biomarker panel for use in the method of Hodko according to the particulars of the assay, such as which organisms were desired to be detected. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
11. Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe, and further in view of either of Reber et al. (US 2023/0311130) or Macemon (US 9,995,742).
The teachings of Hodko and Briscoe are discussed above.
Hodko and Briscoe do not disclose coupling a collection tube with a fluidic device.
Reber discloses coupling a collection tube with a fluidic device. See paragraphs 0025-0028, 0033-0044, 0059-0070, 0079-0082, 0192-0216, 0345, 0349, 0392, and 0468-0487.
Macemon also discloses coupling a collection tube with a fluidic device. See column 2, lines 14-58 and claim 1.
One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe by coupling a collection tube with a fluidic device because both Reber and Macemon disclosed the benefit of transferring a sample to a fluidic device in this manner. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
12. Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe, and further in view of Solczynski et al. (US 2022/0241785).
The teachings of Hodko and Briscoe are discussed above.
Hodko and Briscoe do not disclose use of a valve and valve seat as recited.
Solczynski discloses use of a valve and valve seat in a fluidic device as required in the claim. See paragraphs 0012-0034 and 0045-0147.
One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe by using a valve and valve seat as claimed in a fluidic device because Solczynski disclosed the advantages of such a valve and valve seat in analysis of nucleic acids using a fluidic device. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
13. Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view Briscoe, and further in view of Solczynski and Miller et al. (US 2025/0144623).
The teachings of Hodko, Briscoe, and Solczynski are discussed above.
These documents do not disclose the use of laser welding in forming fluidic devices.
Miller discloses use of laser welding in fluidic devices. See paragraph 0428.
One of ordinary skill in the art would have been motivated to modify the method of Hodko, Briscoe, and Solczynski by applying laser welding to the fluidic device because Miller disclosed the use of laser welding in fluidic devices. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
14. Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe, and either of Reber et al. (US 2023/0311130) or Macemon (US 9,995,742).
Regarding independent claim 13, Hodko discloses a method comprising: loading a blood sample into a fluidic device; performing nucleic acid related processes within the device using beads including nucleic acid extraction and amplification, measuring expression of a composite biomarker, and outputting whether a subject has or does not have an infection, within 60 minutes. See paragraphs 0008-0019, 0029-0030, 0052, 0138, 0141, 0172, 0183, 0186, 0193-0195, 0198, and 0258-0259. Hodko additionally discloses performing LAMP. See paragraph 0183.
Regarding claim 14, Hodko discloses methods which omit the use of DNase and omit performing amplification of genomic DNA (RNA-based detection is disclosed in paragraph 0186).
Hodko does not disclose coupling a collection tube with a fluidic device, or an exact volume of blood volume, such as 600 microliters, or performing nucleic acid amplification in solution after removal from beads.
Briscoe discloses, in the context of nucleic acid analysis within a microfluidic device, removing extracted nucleic acids from beads before amplifying them in solution in another chamber or compartment. See paragraph 0024.
Reber discloses coupling a collection tube with a fluidic device. See paragraphs 0025-0028, 0033-0044, 0059-0070, 0079-0082, 0192-0216, 0345, 0349, 0392, and 0468-0487.
Macemon also discloses coupling a collection tube with a fluidic device. See column 2, lines 14-58 and claim 1.
One of ordinary skill in the art would have been motivated to modify the method of Hodko by first removing target nucleic acids from beads and then amplifying them in solution because Briscoe disclosed that like solid-phase amplification on beads, elution of nucleic acids from beads and amplifying them in solution was conventional in nucleic acid analysis in fluidic devices. One of ordinary skill in the art would have been further motivated to couple a collection tube with a fluidic device because both Reber and Macemon disclosed the benefit of transferring a sample to a fluidic device in this manner. One of ordinary skill in the art would have been motivated to modify the method of Hodko by using a blood sample volume of less than 600 microliters because this would have merely involved routine optimization of known-important reaction parameters, which as well settled in U.S. patent practice does not support unobviousness (M.P.E.P 2144.05). In other words, the skilled artisan would have routinely optimized the blood sample volume in the method of Hodko according to the particulars of the assay, such as which organisms were desired to be detected. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
15. Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe, further in view of either of Reber et al. (US 2023/0311130) or Macemon (US 9,995,742), and further in view of Bommarito et al. (US 2011/0097814).
The teachings of Hodko, Briscoe, Reber, and Macemon are discussed above.
These references do not disclose preparing reagents by convection drying.
Bommarito discloses preparing reagents by convection drying for use in devices. See paragraphs 0116-0117.
One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe and either of Reber or Macemon by preparing dried reagents using convection drying because Bommarito disclosed the advantage of using dried reagents prepared by convection drying. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
16. Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe, further in view of either of Reber et al. (US 2023/0311130) or Macemon (US 9,995,742), and further in view of Wille.
The teachings of Hodko, Briscoe, Reber, and Macemon are discussed above.
These references do not disclose use of an RNA stabilization solution.
Wille discloses use of an RNA stabilization solution. See paragraph 0017.
One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe and either Reber or Macemon by using an RNA stabilization solution because Wille disclosed the advantage of using such a solution in RNA analysis. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
17. Claims 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe, and further in view of either of Reber et al. (US 2023/0311130) or Macemon (US 9,995,742).
The teachings of Hodko, Briscoe, Reber, and Macemon are discussed above.
These references do not disclose the use of the set of informative genes required in claim 17, nor detecting expression of housekeeping and control genes.
One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe, Reber or Macemon by using the gene biomarker panel as recited in claim 17, and using housekeeping and control genes, because these would have merely involved routine optimization of known-important reaction parameters, which as well settled in U.S. patent practice does not support unobviousness (M.P.E.P 2144.05). In other words, the skilled artisan would have routinely optimized the biomarker panel and selection of housekeeping/control genes for use in the method of Hodko according to the particulars of the assay, such as which organisms were desired to be detected. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
18. Claims 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Hodko in view of Briscoe, further in view of either of Reber et al. (US 2023/0311130) or Macemon (US 9,995,742), further in view of Solczynski, and further in view of Miller.
The teachings of Hodko, Briscoe, Reber, and Macemon are discussed above.
These references do not disclose use of a valve and valve seat as recited, nor the use of laser welding.
Solczynski discloses use of a valve and valve seat in a fluidic device as required in the claim. See paragraphs 0012-0034 and 0045-0147.
Miller discloses use of laser welding in fluidic devices. See paragraph 0428.
One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe, and either Reber or Macemon, by using a valve and valve seat in a fluidic device because Solczynski disclosed the advantages of such a valve and valve seat in analysis of nucleic acids using a fluidic device. One of ordinary skill in the art would have been motivated to modify the method of Hodko as modified by Briscoe, Reber or Macemon, and Solczynski, by applying laser welding to the fluidic device because Miller disclosed the use of laser welding in fluidic devices. Regarding claim 20, adjusting the cracking pressure to greater than 10 kPa would have merely involved routine optimization of known-important reaction parameters, which as well settled in U.S. patent practice does not support unobviousness (M.P.E.P 2144.05). It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed method.
CONCLUSION
19. No claims are free of the prior art.
20. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
21. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KENNETH R HORLICK whose telephone number is (571)272-0784. The examiner can normally be reached Mon. - Thurs. 8:30 - 6:30.
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07/28/26
/KENNETH R HORLICK/ Primary Examiner, Art Unit 1681
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