Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Election Restrictions
1. Applicant's election with traverse of Group I and species (2-morpholin-4-ylethanesulfonate; 2’-O-modified riboses; diethyl pyrocarbonate; Mg2+; CRISPR-associated endonucleases or homologs thereof; Cas3) in the reply filed on 3/26/2026 is acknowledged.
The traversal is on the ground(s) that: multiple groups can be searched and examined together without undue burden; considerable time and expense will be saved if all claims can be considered; applicant disagrees with Kellner et al. and Huang et al.
This is not found persuasive because: it is noted that the instant application is a 371 National Stage application and as such is subject to the lack of unity Restriction standard, not a search burden one; further, the cited inventions lack unity for the reasons as indicated in the Restriction Action issued 11/26/2025; as to time and expense, applicant is encouraged to elect the most pertinent invention. Further, applicant has not appeared to indicate more specifically why there is disagreement as to Kellner et al. and Huang et al.
The requirement is still deemed proper and is therefore made FINAL.
Claim 48 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 3/26/2026.
Claims 1-8, 10-12, 24-29, 44, 49 are under consideration.
Information Disclosure Statement
2. The information disclosure statement (IDS) was submitted on 3/17/2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
3. The drawings are objected to because: Figures 10, 11A, 12A-12D recite colors.
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 the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, 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).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
4. Claims 2, 26 are objected to because of the following informalities:
For improved language and clarity, claims 2, 26 should recite “2-morpholin-4-ylethanesulfonate (MES)”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
5. Claims 1-8, 10-12, 24-29, 44, 49 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.
See claims 1-8, 10-12, 24-29, 44, 49 as submitted 3/17/2023.
As to claims 1, 24, the claims recite “nucleic acid of interest”, “either RNA or DNA sequences” and “the amplified nucleic acid of interest”. It is not clear what the relationship is between these nucleic acids as different terminology is used at each step. It is not clear what is again being referred to. Similarly, claims 10 and 29 recite “the isothermally amplified product”. It is not clear what is being referred to as such a recitation lacks express antecedent basis.
Further as to claim 44, claim 44 recites “abnormal”. The term “abnormal” in claim 44 is a relative term which renders the claim indefinite. The term “abnormal” 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.
Further as to claims 44, 49, it is not clear how the general recitations of claim 1 relate to abnormal or exogenous nucleic acid sequences or SARS-CoV-2. It is not clear if the abnormal or exogenous nucleic acid sequences or SARS-CoV-2 are the nucleic acids of interest or not.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
6. Claims 1, 2, 6, 8, 10, 11, 12, 24, 26, 27, 28, 29, 44 are rejected under 35 U.S.C. 103 as being unpatentable over Kellner et al. ("SHERLOCK: nucleic acid detection with CRISPR nucleases," Nature Protocols, Vol. 14: 2986-3012 (2019)) in applicant's IDS submitted 3/17/2023) in view of Huang et al. ("Identification of inhibitors for the DEDDh Family of Exonucleases and a Unique Inhibition Mechanism by Crystal Structure Analysis of CRN 4 Bound with 2 Morpholin 4-ylethanesulfonate (MES)", Journal of Medicinal Chemistry, Vol. 59, No. 17 (2016)) (cited in applicant's IDS submitted 3/17/2023).
See claims 1, 2, 6, 8, 10, 11, 12, 24, 26, 27, 28, 29, 44 as submitted 3/17/2023.
See also the 35 U.S.C. 112(b) rejection above.
Kellner et al. teaches: method of detecting nucleic acid of interest in a sample (abstract)(as recited in claims 1, 24); designing primers complementary to the nucleic acid of interest (p. 7)(as recited in claims 1, 24); performing isothermal amplification to amplify to dsDNA (p. 3)(as recited in claims 1, 24); subjecting amplified nucleic acid to RNA-guided Cas13 (p. 2)(as recited in claims 1, 24); detecting nucleic acid of interest (p. 3)(as recited in claims 1, 24); wherein nucleic acid extractions may result in contamination by nucleases (p. 6); CRISPR-Cas systems (p. 2)(as recited in claims 6, 27); RNA guided (p. 2)(as recited in claims 8, 28); two-step SHERLOCK as well as one-pot reactions (pp. 4-5), as well as multiplex detections, including dual targeting multiplexing (p. 23)(as recited in claims 10, 29); master mix (p. 23)(as recited in claim 11); LwaCas13a (p. 24)(as recited in claim 12); T7 (p. 24)(as recited in claim 12); targeting any sequence or mutation (p. 29) such as SNP (p. 34)(as recited or read upon in claim 44).
Kellner et al. does not teach: protection against nuclease activity (as recited in claims 1, 24).
Huang et al. teaches: compounds could inhibit exonuclease activity of viral proteins; 20 nucleotide RNA were used as substrates for inhibitor coupled nuclease activity assays (p. 8021); including MES, PCMPS, NCA (p. 8022); wherein MES does not interfere with RNA binding activity (p. 8023); suggesting inhibitors for designing nuclease inhibitors for biochemical and biomedical applications (abstract); polynucleotides protected against nuclease activity (inhibitors of exonuclease prevented digestion of 20 nucleotide RNA strands (p. 8021)); MES (as recited in claims 2, 26).
One of ordinary skill in the art would have been motivated to modify the method of Kellner et al. to protect polynucleotides against nuclease activity as taught by Huang et al. Kellner et al. teaches polynucleotides and wherein nucleic acid extractions may result in contamination by nucleases, and Huang et al., which also teaches polynucleotides, teaches the advantage of and solution of protecting polynucleotides against nuclease activity.
One of ordinary skill in the art would have had a reasonable expectation of success for modifying the method of Kellner et al. to protect polynucleotides against nuclease activity as taught by Huang et al. There would have been a reasonable expectation of success given the underlying materials (polynucleotides as taught by Kellner et al. and Huang et al.) and methods are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
7. Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Kellner et al. in view of Huang et al. as applied to claims 1, 2, 6, 8, 10, 11, 12, 24, 26, 27, 28, 29, 44 above, and further in view of Schoenbrunner et al. (“Covalent modification of primers improves PCR amplification specificity and yield,” Biology Methods and Protocols: 1-10 (2017))(See PTO-892: Notice of References Cited).
See claim 3 as submitted 3/17/2023.
See the teachings of Kellner et al. in view of Huang et al. above.
Kellner et al. in view of Huang et al. does not teach: 2’-O-modified riboses.
Schoenbrunner et al. teaches: wherein stable modifications of primer sequences improve the specificity of PCRs; such as 2’-O-methyl ribonucleotides at the 3’ ends of primers enhance PCR specificity (p. 2).
One of ordinary skill in the art would have been motivated to modify as taught by Schoenbrunner et al. with the method as taught by Kellner et al. in view of Huang et al. Kellner et al. in view of Huang et al. teaches use of primers, and Schoenbrunner et al., which also teaches use of primers, teaches the advantage wherein 2’-O-methyl ribonucleotides at the 3’ ends of primers enhance PCR specificity.
One of ordinary skill in the art would have had a reasonable expectation of success for modifying as taught by Schoenbrunner et al. with the method as taught by Kellner et al. in view of Huang et al. There would have been a reasonable expectation of success given the underlying materials (primers as taught by Schoenbrunner et al. and Kellner et al. in view of Huang et al.) and methods are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
8. Claim 4, 5 are rejected under 35 U.S.C. 103 as being unpatentable over Kellner et al. in view of Huang et al. as applied to claims 1, 2, 6, 8, 10, 11, 12, 24, 26, 27, 28, 29, 44 above, and further in view of Kim et al. (WO2019109092A1)(See PTO-892: Notice of References Cited).
See claims 4, 5 as submitted 3/17/2023.
See the teachings of Kellner et al. in view of Huang et al. above.
Kellner et al. in view of Huang et al. does not teach: diethyl pyrocarbonate; divalent cations; Mg²⁺.
Kim et al. teaches: nucleic acid sample preparation agents that inhibit nucleases; including enzyme inhibitors DEP and divalent cations Mg2+ (p. 22).
One of ordinary skill in the art would have been motivated to further use nuclease inhibitors as taught by Kim et al. with the method as taught by Kellner et al. in view of Huang et al. Kellner et al. in view of Huang et al. teaches nucleic acids and protection against nuclease activity, and Kim et al. teaches nuclease inhibitors. One of ordinary skill in the art would have been further motivated to use components as taught by Kim et al. with the method as taught by Kellner et al. in view of Huang et al. to inhibit nucleases for the advantage of preparing nucleic acids and protecting against nuclease activity.
One of ordinary skill in the art would have had a reasonable expectation of success for using nuclease inhibitors as taught by Kim et al. with the method as taught by Kellner et al. in view of Huang et al. There would have been a reasonable expectation of success given the underlying materials and methods (protecting against nucleases as taught by Kim et al. and Kellner et al. in view of Huang et al.) are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
9. Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Kellner et al. in view of Huang et al. as applied to claims 1, 2, 6, 8, 10, 11, 12, 24, 26, 27, 28, 29, 44 above, and further in view of Zhang et al. (WO2019148206A1)(See PTO-892: Notice of References Cited).
See claim 7 as submitted 3/17/2023.
See the teachings of Kellner et al. in view of Huang et al. above. It is noted that Kellner et al. teaches use of CRISPR-Cas systems (p. 3).
Kellner et al. in view of Huang et al. does not teach: Cas3.
Zhang et al. teaches: CRISPR-based diagnostics (abstract); including Cas3 [00182].
One of ordinary skill in the art would have been motivated to use Cas3 as taught by Zhang et al. with the method as taught by Kellner et al. in view of Huang et al. Kellner et al. in view of Huang et al. teaches use of CRISPR-Cas systems, and Zhang et al., which also teaches CRISPR-Cas systems, teaches such a Cas protein for use in CRISPR-Cas systems (See MPEP 2144.06: Substituting equivalents known for the same purpose).
One of ordinary skill in the art would have had a reasonable expectation of success for using Cas3 as taught by Zhang et al. with the method as taught by Kellner et al. in view of Huang et al. There would have been a reasonable expectation of success given the underlying materials (CRISPR-Cas systems as taught by Zhang et al. and Kellner et al. in view of Huang et al.) and methods are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
10. Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Kellner et al. in view of Huang et al. as applied to claims 1, 2, 6, 8, 10, 11, 12, 24, 26, 27, 28, 29, 44 above, and further in view of Skerra et al. (“Phosphorothioate primers improve the amplification of DNA sequences by DNA polymerases with proofreading activity,” Nucleic Acids Research, Vol. No. 14: 3551-3554 (1992))(See PTO-892: Notice of References Cited).
See claim 25 as submitted 3/17/2023.
See the teachings of Kellner et al. in view of Huang et al. above.
Kellner et al. in view of Huang et al. does not teach: phosphorothiolate bonds at the 5' or 3' end to protect against exonuclease activity.
Skerra et al. teaches: wherein introduction of phosphorothioate bonds at 3’ termini of primer can prevent exonuclease attack (abstract).
One of ordinary skill in the art would have been motivated to introduce bonds as taught by Skerra et al. with the method as taught by Kellner et al. in view of Huang et al. Kellner et al. in view of Huang et al. teaches use of primers, and Skerra et al., which also teaches primers, teaches the advantage wherein introduction of phosphorothioate bonds at 3’ termini of primer can prevent exonuclease attack.
One of ordinary skill in the art would have had a reasonable expectation of success for introducing bonds as taught by Skerra et al. with the method as taught by Kellner et al. in view of Huang et al. There would have been a reasonable expectation of success given the underlying materials (primers as taught by Skerra et al. and Kellner et al. in view of Huang et al.) and methods are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
11. Claim 49 is rejected under 35 U.S.C. 103 as being unpatentable over Kellner et al. in view of Huang et al. as applied to claims 1, 2, 6, 8, 10, 11, 12, 24, 26, 27, 28, 29, 44 above, and further in view of Broughton et al. (“CRISPR-Cas12-based detection of SARS-CoV-2,” Nature Biotechnology, Vol. 38: 870-874 (2020))(See PTO-892: Notice of References Cited).
See claim 49 as submitted 3/17/2023.
See also the 35 U.S.C. 112(b) rejection above.
See the teachings of Kellner et al. in view of Huang et al. above. It is noted that Kellner et al. teaches detection and distinction of viruses (p. 4).
Kellner et al. in view of Huang et al. does not teach: detecting SARS-CoV-2.
Broughton et al. teaches: CRISPR-Cas12-based lateral flow assay for detection of SARS-CoV-2 from respiratory swab extracts (p. 870).
One of ordinary skill in the art would have been motivated to use method as taught by Kellner et al. in view of Huang et al. to detect SARS-CoV-2 as taught by Broughton et al. Kellner et al. in view of Huang et al. teaches detection of viruses using CRISPR-Cas systems, and Broughton et al., which also teaches CRISPR-Cas systems, teaches such a virus for detection (See MPEP 2144.06: Substituting equivalents known for the same purpose).
One of ordinary skill in the art would have had a reasonable expectation of success for using method as taught by Kellner et al. in view of Huang et al. to detect SARS-CoV-2 as taught by Broughton et al. There would have been a reasonable expectation of success given the underlying materials and methods (using CRISPR-Cas systems to detect virus as taught by Kellner et al. in view of Huang et al. and Broughton et al.) are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
12. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to M FRANCO G SALVOZA whose telephone number is (571)272-4468. The examiner can normally be reached M-F 8:00 to 5:00.
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/M FRANCO G SALVOZA/Primary Examiner, Art Unit 1672
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