DETAILED ACTION
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 .
Claims Status
Claims 9-15, 18, 60-66, 69, 111, & 112 filed on 05/31/2026 are pending. Claims 17 & 68 are withdrawn from consideration as being drawn to a non-elected invention. Claims 11-13, 15, 18, 62-64, 66, & 69 are currently under examination directed to the elected species of dsDNA and DNA in claims 11, 12, 62, & 63, of blood in claims 13 & 64, of CAS12 complex in claims 15 & 66, and of a restriction enzyme in claims 18 & 69 (see response dated 01/16/2026). The cancellation of claims 16 & 67 and the new claims 111 & 112 in the reply filed on 05/31/2026 is acknowledged. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant application. Response to Applicant’s argument follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 102
Claim(s) 9-14, 18, 60-65, & 69 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Baughman (WO 2020/028180 A1, February 2020).
Regarding amended claim 9, Baughman teaches a method and device for detection (detector device) of nucleic acid target sequences (target biomolecule) comprising a first indicator device including a first indicator sequence that may be cleaved by a Cas protein (primary sensing agent), a first reporter molecule that is a restriction endonuclease (secondary sensing agent), a second indicator device that may be proximal or distal to the first indicator device that includes a second indicator sequence that is cleavable by the first reporter molecule (secondary sensing agent) (contacting activated primary sensing agent with a secondary sensing agent further catalyzing a first reaction that results in activation of said secondary sensing agent) wherein the second indicator sequence is a dsDNA sequence with a target sequence for the restriction endonuclease and the second reporter device (signal agent) may be a nanoparticle or an enzyme that may produce a detectable signal (contacting said activated secondary sensing agent with a signal agent that results in the detection of said signal agent and detecting a signal thereby detecting said target biomolecule using the detector device) (pg. 8 lines 28-31; pg. 10 lines 7-20; pg. 21 lines 5-13; Fig.1; Fig. 3B). Baughman also teaches that the method for determining the presence of a target nucleic acid sequence (target biomolecule) may include a system comprising a device including at least one reporter molecule (comprising a nanoparticle (signal agent)), a solid support, a tether molecule comprising at least one indicator sequence (secondary sensing agent) attaching the indicator sequence (secondary sensing agent) and reporter molecule comprising a nanoparticle (signal agent) to the solid support, an assay compartment, and a detection compartment (device comprises a detector) (secondary sensing agent with a signal agent bound to the surface of a detector) (pg. 2 lines 18-27). Baughman also teaches that the method and device for detection (detector device) of nucleic acid target sequences comprises combining a sample with a Cas protein (primary sensing agent) having a spacer sequence that is complementary to a target nucleic acid of interest (contacting the sample with a primary sensing agent) (pg. 21 lines 5-13).
Regarding claim 10, Baughman teaches the sample may be obtained from various sources comprising biological sources and contains various target nucleic acid sequences (target biomolecule is a biological marker) (pg. 21 lines 25-27).
Regarding claim 11, Baughman teaches the target sequences may be any single-stranded or double-stranded nucleic acid sequence and further that the assay mixture that may comprises an activated Cas protein may be combined with an indicator device to enable detection in which an activated Cas protein cleaves a target nucleic acid sequence selected from single stranded RNA and DNA and double stranded DNA (target biomolecule is selected from dsDNA) (pg. 22 lines 20-21 & 24-28).
Regarding claim 12, Baughman teaches the target sequences may be any single-stranded or double-stranded nucleic acid sequence and further that the assay mixture that may comprises an activated Cas protein may be combined with an indicator device to enable detection in which an activated Cas protein cleaves a target nucleic acid sequence selected from single stranded RNA and DNA and double stranded DNA (target biomolecule comprises a DNA) (pg. 22 lines 20-21 & 24-28).
Regarding claim 13, Baughman teaches the biological sample may include a bodily fluid from a subject comprising a blood sample (biological sample is selected from blood) (pg. 21 lines 25-28 & 32; pg. 22 lines 1-2).
Regarding claim 14, Baughman teaches that the method and device for detection of nucleic acid target sequences comprises combining a sample with a Cas protein (primary sensing agent) having a spacer sequence that is complementary to a target nucleic acid of interest (primary sensing agent comprises a CRISPR enzyme) (pg. 21 lines 5-13).
Regarding claim 18, Baughman teaches a method and device for detection of nucleic acid target sequences (target biomolecule) comprising a first indicator device including a first indicator sequence that may be cleaved by a Cas protein (primary sensing agent), a first reporter molecule that is a restriction endonuclease (secondary sensing agent is a restriction enzyme), a second indicator device that may be proximal or distal to the first indicator device that includes a second indicator sequence that is cleavable by the first reporter molecule (secondary sensing agent is a restriction enzyme) (pg. 8 lines 28-31; pg. 10 lines 7-20; pg. 21 lines 5-13; Fig.1; Fig. 3B).
Regarding amended claim 60, Baughman teaches a method and device for detection (system for detection) of nucleic acid target sequences (target biomolecule) comprising a first indicator device including a first indicator sequence that may be cleaved by a Cas protein (primary sensing agent activatable by the target biomolecule), a first reporter molecule that is a restriction endonuclease (secondary sensing agent), a second indicator device that may be proximal or distal to the first indicator device that includes a second indicator sequence that is cleavable by the first reporter molecule (secondary sensing agent comprising a linker comprising a cleavage site cleavable by the activated primary sensing agent and is activatable by linker cleavage) wherein the second indicator sequence is a dsDNA sequence with a target sequence for the restriction endonuclease and the second reporter device (signal agent) may be a nanoparticle or an enzyme that may produce a detectable signal (a detector capable of sensing the activated secondary sensing agent thereby detecting the presence of said target biomolecule) (pg. 8 lines 28-31; pg. 10 lines 7-20; pg. 21 lines 5-13; Fig.1; Fig. 3B). Baughman also teaches that the method for determining the presence of a target nucleic acid sequence (target biomolecule) may include a system comprising a device including at least one reporter molecule (comprising a nanoparticle (signal agent)), a solid support, a tether molecule comprising at least one indicator sequence (secondary sensing agent) attaching the indicator sequence (secondary sensing agent) and reporter molecule comprising a nanoparticle (signal agent) to the solid support, an assay compartment, and a detection compartment (device comprises a detector) (secondary sensing agent with a signal agent bound to the surface of a detector) (pg. 2 lines 18-27). Baughman also teaches that the method and device for detection (detector device) of nucleic acid target sequences comprises combining a sample with a Cas protein (primary sensing agent) having a spacer sequence that is complementary to a target nucleic acid of interest (contacting the sample with a primary sensing agent) (pg. 21 lines 5-13).
Regarding claim 61, Baughman teaches the sample may be obtained from various sources comprising biological sources and contains various target nucleic acid sequences (target biomolecule is a biological marker) (pg. 21 lines 25-27).
Regarding claim 62, Baughman teaches the target sequences may be any single-stranded or double-stranded nucleic acid sequence and further that the assay mixture that may comprises an activated Cas protein may be combined with an indicator device to enable detection in which an activated Cas protein cleaves a target nucleic acid sequence selected from single stranded RNA and DNA and double stranded DNA (target biomolecule is selected from dsDNA) (pg. 22 lines 20-21 & 24-28).
Regarding claim 63, Baughman teaches the target sequences may be any single-stranded or double-stranded nucleic acid sequence and further that the assay mixture that may comprises an activated Cas protein may be combined with an indicator device to enable detection in which an activated Cas protein cleaves a target nucleic acid sequence selected from single stranded RNA and DNA and double stranded DNA (target biomolecule comprises a DNA) (pg. 22 lines 20-21 & 24-28).
Regarding claim 64, Baughman teaches the biological sample may include a bodily fluid from a subject comprising a blood sample (biological sample is selected from blood) (pg. 21 lines 25-28 & 32; pg. 22 lines 1-2).
Regarding claim 65, Baughman teaches that the method and device for detection of nucleic acid target sequences comprises combining a sample with a Cas protein (primary sensing agent) having a spacer sequence that is complementary to a target nucleic acid of interest (primary sensing agent comprises a CRISPR enzyme) (pg. 21 lines 5-13).
Regarding claim 69, Baughman teaches a method and device for detection of nucleic acid target sequences (target biomolecule) comprising a first indicator device including a first indicator sequence that may be cleaved by a Cas protein (primary sensing agent), a first reporter molecule that is a restriction endonuclease (secondary sensing agent is a restriction enzyme), a second indicator device that may be proximal or distal to the first indicator device that includes a second indicator sequence that is cleavable by the first reporter molecule (secondary sensing agent is a restriction enzyme) (pg. 8 lines 28-31; pg. 10 lines 7-20; pg. 21 lines 5-13; Fig.1; Fig. 3B).
Response to Arguments
The response traverses the rejection. The response asserts that Baughman does not teach, suggest, or motivate “a signal agent bound to a surface of a detector” and, therefore, for at least these reasons, claim 9 patentably distinguishes Baughman. This argument has been thoroughly reviewed but was not found persuasive as Baughman does teach the amended limitation of “a signal bound to a surface of a detector as Baughman teaches that the method for determining the presence of a target nucleic acid sequence (target biomolecule) may include a system comprising a device including at least one reporter molecule (comprising a nanoparticle (signal agent)), a solid support, a tether molecule comprising at least one indicator sequence (secondary sensing agent) attaching the indicator sequence (secondary sensing agent) and reporter molecule comprising a nanoparticle (signal agent) to the solid support, an assay compartment, and a detection compartment (device comprises a detector) (secondary sensing agent with a signal agent bound to the surface of a detector) (pg. 2 lines 18-27) and as further discussed above.
The response also asserts that claim 60 as amended contains similar limitations to claim 9 as amended and thus distinguishes Baughman for at least the above-descried reasons. This argument has been thoroughly reviewed but was not found persuasive for the reasons set forth above.
The response also asserts that each of claims 10-14, 18, 61-65, and 69 depends, directly or indirectly, from claim 1 or claim 60, and as noted above claim 1 is patentably distinguishable over Baughman for at least the reasons above and accordingly, claims 10-14, 18, 61-65, and 69 as amended ae patentably distinguishable over Baughman for at least the reasons discussed above. It is noted that claim 1 is cancelled and discussions of claim 1 is interpreted to be discussions for amended independent claim 9. Further, this argument has been thoroughly reviewed but was not found persuasive for the reasons set forth above.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Claim Rejections - 35 USC § 103
Claim(s) 15 & 66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Baughman (WO 2020/028180 A1, February 2020), in view of Zhang (Zhang et al.; ACS Sensors, Vol. 5, pages 557-562, February 2020).
The teachings of Baughman with respect to claims 9, 14, 60, & 65 are discussed above and incorporated herein.
Regarding claim 15, Baughman does not teach that the CRISPR enzyme comprises a Cas12 complex.
Zhang teaches that RNA-guided CRISPR-associated (Cas) proteins are used for DNA and RNA targeting and detection comprising Cas12a complex programmed with CRISPR RNAs to specifically recognize and cleave double stranded DNA (dsDNA) and can be combined with a biosensor for the detection of dsDNA (pg. 557-558 paragraph bridging pg. 557 & 558 lines 1-28; pg. 558 column 1 1st full paragraph lines 1-6; pg. 558 column 1 2nd full paragraph lines 1-4; pg. 561 column 1 1st full paragraph lines 1-17). Zhang also teaches that detection of DNA with Cas12a complex provides high sensitivity and specificity for molecular diagnostic applications (pg. 557-558 paragraph bridging pg. 557 & 558 lines 23-28; pg. 558 column 1 2nd full paragraph lines 1-4; pg. 561 column 1 1st full paragraph lines 1-17).
Baughman and Zhang are considered to be analogous to the claimed invention because they are all in the same field of use of CRISPR enzymes for nucleic acid detection. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detection of nucleic acid target sequences comprising combining a sample with a Cas protein (primary sensing agent) having a spacer sequence that is complementary to a target nucleic acid of interest (primary sensing agent comprises a CRISPR enzyme) in Baughman to incorporate the use of a Cas12 complex CRISPR enzyme for detection of dsDNA as taught in Zhang because Zhang teaches that doing so would provide high sensitivity and specificity for molecular diagnostic applications.
Regarding claim 66, Baughman does not teach that the CRISPR enzyme comprises a Cas12 complex.
Zhang teaches that RNA-guided CRISPR-associated (Cas) proteins are used for DNA and RNA targeting and detection comprising Cas12a complex programmed with CRISPR RNAs to specifically recognize and cleave double stranded DNA (dsDNA) and can be combined with a biosensor for the detection of dsDNA (pg. 557-558 paragraph bridging pg. 557 & 558 lines 1-28; pg. 558 column 1 1st full paragraph lines 1-6; pg. 558 column 1 2nd full paragraph lines 1-4; pg. 561 column 1 1st full paragraph lines 1-17). Zhang also teaches that detection of DNA with Cas12a complex provides high sensitivity and specificity for molecular diagnostic applications (pg. 557-558 paragraph bridging pg. 557 & 558 lines 23-28; pg. 558 column 1 2nd full paragraph lines 1-4; pg. 561 column 1 1st full paragraph lines 1-17).
Baughman and Zhang are considered to be analogous to the claimed invention because they are all in the same field of use of CRISPR enzymes for nucleic acid detection. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detection of nucleic acid target sequences comprising combining a sample with a Cas protein (primary sensing agent) having a spacer sequence that is complementary to a target nucleic acid of interest (primary sensing agent comprises a CRISPR enzyme) in Baughman to incorporate the use of a Cas12 complex CRISPR enzyme for detection of dsDNA as taught in Zhang because Zhang teaches that doing so would provide high sensitivity and specificity for molecular diagnostic applications.
Claim(s) 111 & 112 is/are rejected under 35 U.S.C. 103 as being unpatentable over Baughman (WO 2020/028180 A1, February 2020), in view of Chao (Chao, Fung, & Guo; IEEE Journal of Selected Topics in Quantum Electronics, Vol. 12, pages 134-142, January 2006).
The teachings of Baughman with respect to claims 9 & 60 are discussed above and incorporated herein.
Regarding new claim 111, Baughman does not teach that detection further comprises using a microring resonator.
Chao teaches the use of microring resonators for sensing and detecting target biomolecules which provides high sensitivity and low detection limits for biomolecules sensing applications while enabling detection of both small and large biomolecules (detection comprises a microring resonator) (abstract lines 1-15).
Baughman and Chao are considered to be analogous to the claimed invention because they are all in the same field of detection of target biomolecules in biological samples. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the presence of a target nucleic acid sequence (target biomolecule) using a system comprising a device including at least one reporter molecule (comprising a nanoparticle (signal agent)), a solid support, a tether molecule comprising at least one indicator sequence (secondary sensing agent) attaching the indicator sequence (secondary sensing agent) and reporter molecule comprising a nanoparticle (signal agent) to the solid support, an assay compartment, and a detection compartment (device comprises a detector) in Baughman to incorporate the use of a microring resonator for detection of target biomolecules as taught in Chao because Chao teaches that doing so would provide high sensitivity and low detection limits for biomolecules sensing applications while enabling detection of both small and large biomolecules.
Regarding new claim 112, Baughman does not teach that the detector comprises a microring resonator.
Chao teaches the use of microring resonators for sensing and detecting target biomolecules which provides high sensitivity and low detection limits for biomolecules sensing applications while enabling detection of both small and large biomolecules (detection comprises a microring resonator) (abstract lines 1-15).
Baughman and Chao are considered to be analogous to the claimed invention because they are all in the same field of detection of target biomolecules in biological samples. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the presence of a target nucleic acid sequence (target biomolecule) using a system comprising a device including at least one reporter molecule (comprising a nanoparticle (signal agent)), a solid support, a tether molecule comprising at least one indicator sequence (secondary sensing agent) attaching the indicator sequence (secondary sensing agent) and reporter molecule comprising a nanoparticle (signal agent) to the solid support, an assay compartment, and a detection compartment (device comprises a detector) in Baughman to incorporate the use of a microring resonator detector for detection of target biomolecules as taught in Chao because Chao teaches that doing so would provide high sensitivity and low detection limits for biomolecules sensing applications while enabling detection of both small and large biomolecules.
Response to Arguments
The response traverses the rejection. The response asserts that each of claims 15, 16, 66, and 67 depends, directly or indirectly from claim 1 or claim 60 and, as noted above, claim 1 and 60 are patentably distinguishable over Baughman for at least the reasons discussed above and therefore claims 15, 16, 66, and 67 is patentably distinguishable over Baughman, at least for the reasons discussed above. Further, the response asserts that Zhang fails to cure the deficiencies of Baughman as the Office has not asserted that Zhang teaches, suggests, or motivates “a signal agent bound to a surface of a detector” and therefore Zhang does not teach, suggest, or motivate this limitation and therefore claims 15, 16, 66, and 67 are patentably distinguish Baughman and Zhang, alone and in combination. This argument has been thoroughly reviewed but was not found persuasive. First, it is noted that claim 1 is cancelled and discussions of claim 1 is interpreted to be discussions for amended independent claim 9. Second, claims 16 & 67 have been cancelled in the reply filed on 05/31/2026. Further, Baughman does teach the amended limitation of “a signal bound to a surface of a detector as Baughman teaches that the method for determining the presence of a target nucleic acid sequence (target biomolecule) may include a system comprising a device including at least one reporter molecule (comprising a nanoparticle (signal agent)), a solid support, a tether molecule comprising at least one indicator sequence (secondary sensing agent) attaching the indicator sequence (secondary sensing agent) and reporter molecule comprising a nanoparticle (signal agent) to the solid support, an assay compartment, and a detection compartment (device comprises a detector) (secondary sensing agent with a signal agent bound to the surface of a detector) (pg. 2 lines 18-27) and as further discussed above. Further, Zhang is not relied upon for teachings of a signal agent bound to a surface of a detector.
The response also asserts that each of new claims 111 & 112 depends, directly or indirectly, from claim 1 or claim 60 and, as noted above, claims 1 and 60 are patentably distinguishable over Baughman and Zhang for at least the reasons discussed above and, accordingly claims 111 and 112 is patentably distinguishable over Baughman and Zhang, alone and in combination, at least for the reasons discussed above. This argument has been thoroughly reviewed but was not found persuasive. First, it is noted that claim 1 is cancelled and discussions of claim 1 is interpreted to be discussions for amended independent claim 9. Second, the limitations of new claims 111 & 112 are taught over Baughman in view of Chao, applied as necessitated by amendment and as discussed further above.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Conclusion
Claims 9-15, 18, 60-66, 69, 111, & 112 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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