Prosecution Insights
Last updated: April 19, 2026
Application No. 18/260,029

SPECIFIC DETECTION OF NUCLEIC ACID SEQUENCES USING ACTIVATE CLEAVE & COUNT (ACC) TECHNOLOGY

Non-Final OA §103
Filed
Jun 29, 2023
Examiner
BOESEN, AGNIESZKA
Art Unit
1672
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The Board Of Trustees Of The University Of Illinois
OA Round
1 (Non-Final)
68%
Grant Probability
Favorable
1-2
OA Rounds
3y 4m
To Grant
90%
With Interview

Examiner Intelligence

Grants 68% — above average
68%
Career Allow Rate
555 granted / 816 resolved
+8.0% vs TC avg
Strong +22% interview lift
Without
With
+22.5%
Interview Lift
resolved cases with interview
Typical timeline
3y 4m
Avg Prosecution
31 currently pending
Career history
847
Total Applications
across all art units

Statute-Specific Performance

§101
6.9%
-33.1% vs TC avg
§103
31.6%
-8.4% vs TC avg
§102
20.7%
-19.3% vs TC avg
§112
21.3%
-18.7% vs TC avg
Black line = Tech Center average estimate • Based on career data from 816 resolved cases

Office Action

§103
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 . Preliminary amendment filed on December 6, 2022 is acknowledged. Claims 1-20 are pending and under examination in this Office action. Information Disclosure Statement The information disclosure statement (IDS) submitted on December 6, 2022 has been considered by the examiner. Claim Rejections - 35 USC § 103 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. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. Claims 1-7, and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US Patent Application Publication 2020/0254443 in view of Cunningham et al. (US Application Publication US 2009/0264314). Regarding Claim 1. Zhang et al. teach a system for detecting nucleic acids in a sample (Para. [0143], a nucleic acid detection system; Para. [0144], these systems may be referred to herein as SHERLOCK systems and the reactions they facilitate as SHERLOCK reactions), comprising: a first molecule with a second molecule bound to a surface of the first molecule by nucleotide tethers (Para. [0006], cleavable reporter construct comprising a first molecule and a second molecule linked by an RNA or DNA linker the first molecule may be FITC the first binding agent may be an antibody, such as an anti-FITC antibody for example, which is fixed or otherwise immobilized); an assay medium comprising a guide polynucleotide sequence and a Cas enzyme, wherein the guide polynucleotide sequence and the Cas enzyme are capable of forming a CRISPR/Cas complex when exposed to a sample containing a target nucleotide sequence (Para. [0143], a nucleic acid detection system comprising a CRISPR system, one or more guide RNAs designed to bind to corresponding target molecules, a reporter construct); a biosensor (Para. [0143], a detection agent that specifically binds the second molecule; Para. [0148], Such binding pairs are known to those skilled in the art and include, but are not limited to, antibody-antigen pairs, enzyme-substrate pairs, receptor-ligand pairs, and streptavidin-biotin); wherein the guide polynucleotide sequence binds the target nucleotide sequence and Cas enzyme thereby forming the CRISPR/Cas complex; wherein the Cas enzyme is configured to cleave the nucleotide tethers thereby releasing the second molecule (Para. [0144], If a target molecule is present in a sample, the corresponding guide molecule will guide the CRSIPR Cas/guide complex to the target molecule by hybridizing with the target molecule, thereby triggering the CRISPR effector protein's nuclease activity. Zhang et al. fail to explicitly disclose a second molecule comprising streptavidin linked nanoparticles; a biosensor comprising a biotinylated biosensor; an imaging platform; wherein the streptavidin linked nanoparticles bind the biotinylated biosensor, and wherein the imaging platform is configured to quantify the number of streptavidin linked nanoparticles bound to the biotinylated biosensor. Cunningham et al. teach label-free detection of biomolecular interactions (Title and Abstract) and teaches a first molecule comprising a source substrate (Paragraphs [0242]-[0247], Example 8 Immobilization of One or More Specific Binding Substances After following the above protocol for activating the biosensor with amine, a linker molecule can be attached to the biosensor Protocol for Activating Amine-Coated Biosensor with Biotin The resulting biosensors can be used for capturing avidin or strepavidin molecules); a second molecule comprising streptavidin linked nanoparticles (Para. [0154], as shown in FIG. 7C, nanoparticles that are covalently coated with streptavidin); a biosensor comprising a biotinylated biosensor (Para. [0154], biotin-tagged binding partners on the biosensor surface); an imaging platform (Para. [0016], a detection system comprising a biosensor or optical device of the invention, a light source that directs light to the biosensor or optical device, and a detector that detects light reflected from the biosensor); wherein the streptavidin linked nanoparticles bind the biotinylated biosensor (Para. [0153], Where the tag is biotin, the biotin molecule will binds strongly with streptavidin; Para. [0154], Binding of a large bead will result in a large change in the optical density upon the biosensor surface, and an easily measurable signal); and wherein the imaging platform is configured to quantify the number of streptavidin linked nanoparticles bound to the biotinylated biosensor (Para. [0177], Biosensors of the invention are also capable of detecting and quantifying the amount of a binding partner from a sample that is bound to a biosensor array distinct location by measuring the shift in reflected wavelength of light). It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to modify Broad with optical technique to detect biomolecular interactions taught by Cunningham for the purpose of measuring a detectable signal (Broad, Abstract). Regarding Claim 2. Zhang fails to explicitly disclose wherein the substate source is a biologically inert solid material. Cunningham is in the field of label-free detection of biomolecular interactions (Title and Abstract) and teaches the substate source is a biologically inert solid material (Para. [0251], Table 2 demonstrates an example of the sequence of steps that are used to prepare and use a biosensor, and various options that are available for Surface activation chemistry, chemical linker molecules, specific binding substances and binding partners molecules; Table 2, Col. 1, Bare Sensor, Row 1, Glass). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Broad with optical technique to detect biomolecular interactions taught by Cunningham for the purpose of measuring a detectable signal (Broad, Abstract). Regarding Claims 3 and 4. Zhang fails to explicitly disclose wherein the inert solid material is glass (silicon oxide) or solid material being polyester. Cunningham teaches the inert solid material is glass (silicon oxide) (Para. [0251], Table 2 demonstrates an example of the sequence of steps that are used to prepare and use a biosensor, and various options that are available for Surface activation chemistry, chemical linker molecules, specific binding Substances and binding partners molecules; as well as polyester Table 2, Col. 1, Bare Sensor, Row 1, Glass). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Zhang with optical technique to detect biomolecular interactions taught by Cunningham for the purpose of measuring a detectable signal (see Abstract). Regarding Claim 5. Zhang fails to explicitly disclose wherein the inert solid material is gold or silver. Cunningham is in the field of label-free detection of biomolecular interactions (Title and Abstract) and teaches the inert solid material is gold or silver (Para. [0162], a reflective material that is coated onto the first surface of a sheet material of a SRVD biosensor. A reflective material can be, for example silver, aluminum, or gold). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Zhang and Cunningham with optical technique to detect biomolecular interactions taught by Cunningham for the purpose of measuring a detectable signal (see Abstract). Regarding Claim 6. Zhang fails to explicitly disclose wherein the inert solid material is silicon nitride or titanium oxide. Cunningham teaches the inert solid material is silicon nitride or titanium oxide (Para. [0112], a layer of silicon nitride with a thickness of about 120 nm can be sputter deposited onto the surface of the optical sensor. Other coatings, such as (without limitation) zinc sulfide, titanium dioxide, or tantalum oxide may be sputter deposited onto the grating as well). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Broad with optical technique to detect biomolecular interactions taught by Cunningham for the purpose of measuring a detectable signal. Regarding Claim 7. Zhang discloses the system of claim 1, wherein the Cas is Cas 9, Cas12a, Cas12b, or Cas13 (Para. [0011], the assay or device may comprise multiple Cas 13 orthologs, multiple Cas12 orthologs, or a combination of Cas13 and Cas12 orthologs). Regarding Claim 9. Zhang discloses the system of claim 1, wherein the target nucleotide sequence is indicative of cancer (Para. [0528], With SHERLOCKv1, we validated the technology on cell-free DNA standards to show detection of cancer mutations We also designed a SHERLOCK assay to detect a typical EGFR exon 19 deletion (5 amino acids) involved in lung cancer and found that SHERLOCK could both sensitively detect this genomic alteration via fluorescence (FIG. 86J and FIG. 90A) and on the lateral flow strips (FIG. 86K, L and FIG. 90B, C). Regarding Claim 10, Zhang discloses the system of claim 9, wherein the cancer is a solid tumor (Para. [0528], we validated the technology on cell-free DNA standards to show detection of cancer mutations We also designed a SHERLOCK assay to detect a typical EGFR exon 19 deletion (5 amino acids) involved in lung cancer and found that SHERLOCK could both sensitively detect this genomic alteration via fluorescence (FIG. 86J and FIG. 90A) and on the lateral flow strips (FIG. 86K, L and FIG. 90B, C)). Regarding Claim 11, modified Broad discloses the system of claim 10, wherein the cancer is a blood-based cancer (Para. [0427], Thus, it is advantageous to detect of LOH markers in a subject suffering from or at risk of cancer. The present invention may be used to detect LOH in tumor cells. In one embodiment, circulating tumor cells may be used as a biological sample). Regarding Claim 17, Zhang fails to explicitly disclose wherein the biosensor comprises a waveguide structure through which light travels laterally. Cunningham teaches the biosensor comprises a waveguide structure through which light travels laterally (Para. [0192], Another method of detection involves the use of a beam splitter that enables a single illuminating fiber, which is connected to a light source, to be oriented at a 90 degree angle to a collecting fiber, which is connected to a detector. Light is directed through the illuminating fiber probe into the beam splitter, which directs light at the biosensor. The reflected light is directed back into the beam splitter, which directs light into the collecting fiber probe. An example of such a detection device is shown in FIG. 20). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Zhang with optical technique to detect biomolecular interactions taught by Cunningham for the purpose of measuring a detectable signal. Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US Patent Application Publication 2020/0254443 in view of Cunningham et al. (US Application Publication US 2009/0264314) as applied to claim 1 and further in view of Broughton et al. (Nature Biotechnology April 2020, p. 870-875). Zhang and Cunningham teach the claimed invention as discussed above. They do not teach detecting SARS-CoV-2 using their method. Broughton et al. teach detecting SARS-CoV-2 with CRISPR/Cas. It would have been prima facie obvious to detect SARS-CoV-2 with the method of Zhang and Cunningham because Broughton et al. teach successful application of CRISPR/Cas in detection of SARS-CoV-2 (see Figure 2 and Table 1). Claims 12-14 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US Patent Application Publication 2020/0254443 in view of Cunningham et al. (US Application Publication US 2009/0264314), as applied to claim 1 and further in view of Fang et al. (US 2011/0246078). Zhang and Cunningham teach the claimed invention as discussed above. Regarding Claim 12 Zhang fails to explicitly disclose wherein the biosensor comprises a photonic crystal, and wherein the imaging platform comprises a light source configured to excite a resonance of the photonic crystal and a detector configured to detect light reflected from the photonic crystal. Fang teaches methods using label-free biosensors to identify compounds of interest (Para. [0003]) and teaches the biosensor comprises a photonic crystal, and wherein the imaging platform comprises a light source configured to excite a resonance of the photonic crystal and a detector configured to detect light reflected from the photonic crystal (Paras. [0063] and [0064], 9. Optical Biosensors for RWG biosensor including photonic crystal biosensors, the readout is the resonance angle or wavelength at which a maximum in coupling efficiency is achieved. The resonance angle or wavelength is a function of the local refractive index at or near the sensor surface; Para. [0065], The commercial system consists of a temperature-control unit, an optical detection unit). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Zhang and Cunningham and to use of optical biosensors taught by Fang for the purpose of measuring a detectable signal. Regarding Claim 13. Zhang fails to explicitly disclose wherein the imaging platform is configured to quantify a resonant peak intensity value measured on a pixel-by-pixel basis across the photonic crystal. Fang is in the field of methods using label-free biosensors to identify compounds of interest (Para. [0003]) and teaches the imaging platform is configured to quantify a resonant peak intensity value measured on a pixel-by-pixel basis across the photonic crystal (Paras. [0085] and [0086], a. Biosensor Output Parameters Other biosensor output parameters can be obtained from a resonant peak. For example, peak position, intensity, peak shape and peak width at half maximum (PWHM) can be used; Paras. [0115] and [0116], (3). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Broad with the use of optical biosensors taught by Fang for the purpose of measuring a detectable signal. Regarding Claim 14. Zhang fails to explicitly disclose wherein the imaging platform comprises a non-imaging detection instrument. Fang is in the field of methods using label-free biosensors to identify compounds of interest (Para. [0003]) and teaches the imaging platform comprises a non-imaging detection instrument (Para. [0145], Label-free cell-based assays generally employ a biosensor A biosensor typically utilizes a transducer such as an optical, electrical, calorimetric, acoustic, magnetic, or like transducer, to convert into a quantifiable signal. The biosensors that are applicable to the present invention include, but not limited to, optical biosensor systems such as surface plasmon resonance (SPR) and resonant waveguide grating (RWG) biosensors, resonant mirrors, or ellipsometer, and electric biosensor systems such as bioimpedance systems). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Broad with the use of optical biosensors taught by Fang for the purpose of measuring a detectable signal. Regarding Claim 20, Zhang fails to explicitly disclose wherein the biosensor is a surface plasmon resonant biosensor. Fang teaches the biosensor is a surface plasmon resonant biosensor (Para. [0145], Label-free cell-based assays generally employ a biosensor A biosensor typically utilizes a transducer such as an optical, electrical, calorimetric, acoustic, magnetic, or like transducer, to convert into a quantifiable signal. The biosensors that are applicable to the present invention include, but not limited to, optical biosensor systems such as surface plasmon resonance (SPR) and resonant waveguide grating (RWG) biosensors, resonant mirrors, or ellipsometer, and electric biosensor systems such as bioimpedance systems). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Broad with the use of optical biosensors taught by Fang for the purpose of measuring a detectable signal. Claims 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US Patent Application Publication 2020/0254443 in view of Cunningham et al. (US Application Publication US 2009/0264314), as applied to claim 1 and further in view of Poetter et al. (US Patent Application Publication US 2013/0189706). Regarding Claim 15. Zhang and Cunningham fail to explicitly disclose wherein the biosensor is a whispering gallery mode biosensor. Poetter is in the field of biosensors to detect target analytes (Abstract) and teaches the biosensor is a whispering gallery mode biosensor (Abstract, biosensor is formed from microspheroidal particles which have had a binding partner for the target analyte immobilized on their surfaces. The binding partners may be nucleotides; peptides, proteins, enzymes, antibodies and so on. When the analyte binds to its partner, the whispering gallery mode (WGM) profiles of the micro spheroidal particles change such that the profile peaks undergo a red- or blue-shift). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Broad with the method of detecting a target analyte taught by Poetter for the purpose of for the purpose of measuring a detectable signal. Regarding Claim 16, Zhang and Cunningham, fail to explicitly disclose wherein the whispering gallery biosensor is a ring resonator, microtoroid, or microsphere. Poetter is in the field of biosensors to detect target analytes (Abstract) and teaches the whispering gallery biosensor is a ring resonator, microtoroid, or microsphere (Abstract, biosensor is formed from microspheroidal particles which have had a binding partner for the target analyte immobilized on their surfaces. The binding partners may be nucleotides; peptides, proteins, enzymes, antibodies and so on. When the analyte binds to its partner, the whispering gallery mode (WGM) profiles of the micro spheroidal particles change such that the profile peaks undergo a red- or blue-shift). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Zhang and with the method of detecting target analyte taught by Poetter for the purpose of measuring a detectable signal. Claims 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US Patent Application Publication 2020/0254443 in view of Cunningham et al. (US Application Publication US 2009/0264314), as applied to claim 1 and further in view of Oraevsky et (US Application Publication US 2005/0175540). Regarding Claim 18, fails to explicitly disclose wherein the biosensor is an acoustic biosensor. Oraevsky is in the field of optoacoustical imaging (Title) and teaches the biosensor is an acoustic biosensor (Para. [0265], breast cancer cells can be (1) successfully targeted by biotinylated Herceptin antibody, (2) further targeted with 40-nm gold nanoparticles conjugated with streptavidin, and (3) detected and imaged with laser optoacoustic imaging; Para. [252], A schematic diagram of the bio-warfare detection technology is depicted in FIG. 9A. The measurement procedure with the optoacoustic nanobiosensor A sample of aerosols or water suspected to contain bio-warfare agents, e.g. DMO, is collected and mixed in water with gold nanoparticles (NP) 14 conjugated to a monocional antibody (mAB)). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Zhang with the photoacoustic biosensor taught by Oraevsky of for the purpose of measuring a detectable signal. Regarding Claim 19, modified Broad discloses the system of claim 1. Broad fails to explicitly disclose wherein the biosensor is a photoacoustic biosensor. Oraevsky is in the field of optoacoustical imaging (Title) and teaches the biosensor is a photoacoustic biosensor (Para. [0265], breast cancer cells can be (1) successfully targeted by biotinylated Herceptin antibody, (2) further targeted with 40-nm gold nanoparticles conjugated with streptavidin, and (3) detected and imaged with laser optoacoustic imaging; Para. [252]. It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Broad with the photoacoustic biosensor taught by Oraevsky of for the purpose of measuring a detectable signal. Thus, the present invention would have been prima facie obvious at the time the invention was made. Contact Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to AGNIESZKA BOESEN whose telephone number is (571)272-8035. The examiner can normally be reached on 8:30 - 5:00 PM. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /AGNIESZKA BOESEN/Primary Examiner, Art Unit 1648
Read full office action

Prosecution Timeline

Jun 29, 2023
Application Filed
Jan 10, 2026
Non-Final Rejection — §103 (current)

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Prosecution Projections

1-2
Expected OA Rounds
68%
Grant Probability
90%
With Interview (+22.5%)
3y 4m
Median Time to Grant
Low
PTA Risk
Based on 816 resolved cases by this examiner. Grant probability derived from career allow rate.

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