Prosecution Insights
Last updated: May 29, 2026
Application No. 18/051,344

DNA-DYE ASSEMBLY BASED SINGLE-MOLECULE FLUORESCENCE LIFETIME IMAGING PROBES

Non-Final OA §102§103§112
Filed
Oct 31, 2022
Priority
Nov 01, 2021 — provisional 63/274,457
Examiner
RILEY, JEZIA
Art Unit
1681
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Massachusetts Institute Of Technology
OA Round
1 (Non-Final)
83%
Grant Probability
Favorable
1-2
OA Rounds
0m
Est. Remaining
90%
With Interview

Examiner Intelligence

Grants 83% — above average
83%
Career Allowance Rate
1085 granted / 1304 resolved
+23.2% vs TC avg
Moderate +7% lift
Without
With
+6.9%
Interview Lift
resolved cases with interview
Typical timeline
2y 5m
Avg Prosecution
23 currently pending
Career history
1323
Total Applications
across all art units

Statute-Specific Performance

§101
1.5%
-38.5% vs TC avg
§103
39.5%
-0.5% vs TC avg
§102
23.8%
-16.2% vs TC avg
§112
12.8%
-27.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1304 resolved cases

Office Action

§102 §103 §112
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 . Election/Restrictions Applicant’s election without traverse of Group I in the reply filed on 11/05/2025 is acknowledged. 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. Claims 6-7 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. Claim 6 is vague and indefinite because it is unclear what is meant by “a biological or non-biological material”. Is the biological material another DNA assembly or something else? and is the non-biological material a solid support or another chromophore or something else? No clear definition was provided in the specification. Claim 7 is vague and indefinite because it is unclear what are the metes and bound for the terms “operably coupled”. Note that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. Also see In re Van Geuns, 988 F.2d 1181,26 USPQ2d 1057 (Fed. Cir. 1993). Also see, In re Zetz, 13 USPQ2d 1320,1322. “An essential purpose of patent examination is to fashion claims that are precise, clear, correct and unambiguous.” Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim(s) 1-6, 8-10, 16-17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yurke et al. US 20190048036. Yurke et al. discloses a complex quantum circuit for quantum computing, comprising: at least two chromophores; and at least one nucleotide oligomer, wherein said at least two chromophores is bound to said at least one nucleotide oligomer, and wherein said at least two chromophores are nanospaced apart along said nucleotide oligomer. Yurke et al. have created compositions of one or more chromophores attached to a nucleotide architecture. When two or more chromophores are spaced close enough in which an exciton is transferred from one chromophore to another without energy loss (nanospaced) within the nucleotide architecture they can propagate excitons down quantum wires and through quantum circuits, which can be used in quantum computing; the chromophores are attached to a nucleotide architecture to make exciton wires and the nucleotide architecture configures the exciton wires into gates or switches. In some embodiments, the nucleotide architecture is double stranded or the nucleotide architecture is single stranded... In other embodiments the nucleotide architecture is two- or three-dimensional to allow for more complex circuits or to increase rigidity of the chromophores within the architecture. In other embodiments the nucleotide strands comprising the architecture may be branched to allow for increased complexity of the structure. In further embodiments, the nucleotide strands are configured by nucleotide origami. In other further embodiments, the nucleotide strands are configured into nucleotide bricks allowing for very complex and controlled three-dimensional structures. (Brief Summary of the Invention). (This is viewed to be inclusive of the nucleic acid assembly/nucleic acid scaffold) Yurke et al. discloses “When chromophores aggregates in high concentrations in solution excitonic quantum coherent behavior (e.g. large Davydov splitting, exchange narrowing, circular dichroism, Cotton effects, or Stokes shifting) can be observed. When excited, the chromophore may emit an exciton, an electron and electron hole pair. If two chromophores are sufficiently close to each other, the emitted exciton may be transmitted from the excited chromophore to the neighboring chromophore without a loss in energy” [0060] (this is viewed as the alteration of the photophysical property of the adjacent chromophores of claims 8-10). Yurke et al. teaches “Any method of designing the architectures and self-assembly may be used, such as but not limited to nucleotide origami, nucleotide brick molecular canvases, single stranded tile techniques, or any other method of nucleotide folding or nanoassembly such as, but not limited to, using nucleotide tiles, nucleotide scaffolds, nucleotide lattices, four-armed junction, double-crossover structures” [0047] (this is viewed to be inclusive of claim 2). Yurke et al. teaches FIG. 1A is a schematic representation of a simple three-way branched nucleotide brick bringing together two other bricks with the chromophore bound to their 5′ ends. FIG. 1B is a schematic representation of a simple nucleotide brick bringing together two chromophore bound separate bricks, one with a chromophore bound to the 3′ end and the other to the 5′ end. FIG. 1C is a schematic representation of two simple nucleotide bricks, either bound with a chromophore, with the chromophore bound internally in both bricks. FIGS. 1A-1C show the chromophore bound to the same nucleotide duplex. FIG. 1D is a schematic representation of a canvas with two of the bricks bound with a chromophore internally and on different nucleotide duplexes [0019]… Taken together, by altering the composition of the solution surrounding the nucleotide architecture and by altering the distance between the chromophores, one skilled in the art may alter the absorbance and emission spectra for two or more chromophores bound to a nucleotide architecture to fine tune toward dimer type [0069] (this is viewed to be inclusive of “wherein the change in nucleic acid assembly is a change in length of a nucleic acid hybrid in the nucleic acid scaffold that is opposite the adjacent chromophores in claims 1-2 and wherein the correct assembly of a scaffold produces the change in the nucleic acid assembly of claim 16). Yurke et al. teaches the at least two nucleotide brick molecular canvases each comprise between 1 and about 5,000 bricks; the bricks comprise one or more of RNA, DNA, LNA, PNA, and/or UNA (this is viewed to be inclusive of claim 5) and are about 24 to about 42 nucleotides in length; at least one chromophore is asymmetrical; and said nucleotide brick molecular canvases further comprises one or more of one-, two-, and/or three-dimensional sections; at least one of said chromophores is covalently bound to a linker nucleotide oligomer and wherein said linker nucleotide oligomer Watson-Crick pairs with a brick within the nucleotide brick molecular canvas. (See claims). In some embodiments, the architecture is attached to a substrate, such as a glass slide, a silicon base, or a breadboard [0058]. (this is viewed to be inclusive of claim 6). Yurke et al. teaches “Any chromophore that emits an exciton when excited is acceptable may be used in any embodiment. A chromophore may be symmetrical or preferably asymmetrical” (see [0020], [0061] and claims) (this is viewed to be inclusive of claims 3-4). Yurke et al. teaches “The orientation on a linear oligomer, which affects the absorbance spectra, is also affected by characteristics of the solution, including salt concentration (FIG. 3A), temperature (FIG. 3C), and cation concentration. Therefore, by altering the conditions of the solution, it is possible to fine tune the absorbance spectra multiple chromophores nanospaced from each other. As shown in FIGS. 3A and 3B, as the salt concentration increases, a chromophore dimer may be fine-tuned to exhibit either J-dimer characteristics at lower salt concentrations or H-dimer characteristics at high salt concentrations. FIG. 3C further shows that by altering both the temperature and salt concentrations, it is further possible to tune the chromophores for specific characteristics. FIG. 3D shows that not only the absorbance, but the emission is altered by changing the concentration of salt in the solution” [0067] (this is viewed to be inclusive of claims 9 and 17, wherein the excited state lifetime of the adjacent chromophores is altered by a change in solvent polarity, because polarity (dielectric constant) decreases with increasing salt concentration due to ion-induced structural changes in water). Claim(s) 1-6, 8, 10 and 16 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Hart et al. (Chem., Vol. 7, No. 3, 1, March 11, 2021, pp. 752-773; cited in IDS filed 07/03/2024). The applied reference has a common inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. Hart et al. discloses a DNA-based platform that spatially organizes cyanine chromophores to construct tunable excitonic systems. They synthesized DNA-chromophore nanostructures (abstract, page 765) (this is viewed to be inclusive of claims 1 and 5). Hart et al. synthesized DNA strands with covalently attached, sequential indocarbocyanine Cy3 chromophores (this is viewed to be inclusive of claims 3-4) that they used to fabricate DNA duplexes and higher-order structures with chromophores positioned at desired spatial locations. They characterized the chromophore-DNA constructs with two-dimensional (2D) electronic spectroscopy, single-molecule spectroscopy, and computational modeling. With these constructs, they demonstrated both systematic variation in electronic coupling and aggregate lengths and also scaffold-dependent system-bath coupling. Upon increasing the rigidity of the DNA scaffold, the efficiency of energy transfer to an acceptor chromophore decreased, experimentally demonstrating the way in which the bath can tune the steps underlying long-distance exciton transport (page 753). In pages 754-764, Hart et al. discloses determination of photophysical properties of the adjacent chromophores in a DNA assembly/scaffold (this is viewed as the alteration of the photophysical property of the adjacent chromophores of claims 1, 8). For example, Hart et al. discloses variation of the electronic coupling within the Cy3 dimer constructs by changing the distance and relative orientation between the two chromophores (this is viewed to be inclusive of the change of length of a nucleic acid hybrid of claims 1-2); they show that the dimer without nucleotide spacers shows a dramatic redistribution of oscillator strength; …when the Cy3 dimers were separated by three nucleotide spacers, the oscillator strength of the 0–0 band was recovered near the level of the Cy3 monomer (page 756 and Figure 2)…. Hart et al. investigated scaffold-dependent behavior, and compared the ultrafast system-bath coupling of free Cy3, Cy3 monomer in duplexes, and Cy3 monomer in DX tiles (this is viewed to be inclusive of the DX tile of claim 2) (page 758 and Figure 3)… Hart et al. investigated energy transfer efficiency on DNA scaffold, from Cy3 monomer or dimer to the Cy5 acceptor (pages 762-764) (this is viewed to be inclusive of claims 10 and 16). 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. 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. Claim(s) 1-13, 16-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yurke et al. US 20190048036 in view of Mikkila et al. Nano Lett. 2014, 14, pp.2196-2200. Yurke et al. discloses a complex quantum circuit for quantum computing, comprising: at least two chromophores; and at least one nucleotide oligomer, wherein said at least two chromophores is bound to said at least one nucleotide oligomer, and wherein said at least two chromophores are nanospaced apart along said nucleotide oligomer. Yurke et al. have created compositions of one or more chromophores attached to a nucleotide architecture. When two or more chromophores are spaced close enough in which an exciton is transferred from one chromophore to another without energy loss (nanospaced) within the nucleotide architecture they can propagate excitons down quantum wires and through quantum circuits, which can be used in quantum computing; the chromophores are attached to a nucleotide architecture to make exciton wires and the nucleotide architecture configures the exciton wires into gates or switches. In some embodiments, the nucleotide architecture is double stranded or the nucleotide architecture is single stranded... In other embodiments the nucleotide architecture is two- or three-dimensional to allow for more complex circuits or to increase rigidity of the chromophores within the architecture. In other embodiments the nucleotide strands comprising the architecture may be branched to allow for increased complexity of the structure. In further embodiments, the nucleotide strands are configured by nucleotide origami. In other further embodiments, the nucleotide strands are configured into nucleotide bricks allowing for very complex and controlled three-dimensional structures. (Brief Summary of the Invention). (This is viewed to be inclusive of the nucleic acid assembly/nucleic acid scaffold) Yurke et al. discloses “When chromophores aggregates in high concentrations in solution excitonic quantum coherent behavior (e.g. large Davydov splitting, exchange narrowing, circular dichroism, Cotton effects, or Stokes shifting) can be observed. When excited, the chromophore may emit an exciton, an electron and electron hole pair. If two chromophores are sufficiently close to each other, the emitted exciton may be transmitted from the excited chromophore to the neighboring chromophore without a loss in energy” [0060] (this is viewed as the alteration of the photophysical property of the adjacent chromophores of claims 8-10). Yurke et al. teaches “Any method of designing the architectures and self-assembly may be used, such as but not limited to nucleotide origami, nucleotide brick molecular canvases, single stranded tile techniques, or any other method of nucleotide folding or nanoassembly such as, but not limited to, using nucleotide tiles, nucleotide scaffolds, nucleotide lattices, four-armed junction, double-crossover structures” [0047] (this is viewed to be inclusive of claim 2). Yurke et al. teaches FIG. 1A is a schematic representation of a simple three-way branched nucleotide brick bringing together two other bricks with the chromophore bound to their 5′ ends. FIG. 1B is a schematic representation of a simple nucleotide brick bringing together two chromophore bound separate bricks, one with a chromophore bound to the 3′ end and the other to the 5′ end. FIG. 1C is a schematic representation of two simple nucleotide bricks, either bound with a chromophore, with the chromophore bound internally in both bricks. FIGS. 1A-1C show the chromophore bound to the same nucleotide duplex. FIG. 1D is a schematic representation of a canvas with two of the bricks bound with a chromophore internally and on different nucleotide duplexes [0019]… Taken together, by altering the composition of the solution surrounding the nucleotide architecture and by altering the distance between the chromophores, one skilled in the art may alter the absorbance and emission spectra for two or more chromophores bound to a nucleotide architecture to fine tune toward dimer type [0069] (this is viewed to be inclusive of “wherein the change in nucleic acid assembly is a change in length of a nucleic acid hybrid in the nucleic acid scaffold that is opposite the adjacent chromophores in claims 1-2 and wherein the correct assembly of a scaffold produces the change in the nucleic acid assembly of claim 16). Yurke et al. teaches the at least two nucleotide brick molecular canvases each comprise between 1 and about 5,000 bricks; the bricks comprise one or more of RNA, DNA, LNA, PNA, and/or UNA (this is viewed to be inclusive of claim 5) and are about 24 to about 42 nucleotides in length; at least one chromophore is asymmetrical; and said nucleotide brick molecular canvases further comprises one or more of one-, two-, and/or three-dimensional sections; at least one of said chromophores is covalently bound to a linker nucleotide oligomer and wherein said linker nucleotide oligomer Watson-Crick pairs with a brick within the nucleotide brick molecular canvas. (See claims). In some embodiments, the architecture is attached to a substrate, such as a glass slide, a silicon base, or a breadboard [0058]. (this is viewed to be inclusive of claim 6). Yurke et al. teaches “Any chromophore that emits an exciton when excited is acceptable may be used in any embodiment. A chromophore may be symmetrical or preferably asymmetrical” (see [0020], [0061] and claims) (this is viewed to be inclusive of claims 3-4). Yurke et al. teaches “The orientation on a linear oligomer, which affects the absorbance spectra, is also affected by characteristics of the solution, including salt concentration (FIG. 3A), temperature (FIG. 3C), and cation concentration. Therefore, by altering the conditions of the solution, it is possible to fine tune the absorbance spectra multiple chromophores nanospaced from each other. As shown in FIGS. 3A and 3B, as the salt concentration increases, a chromophore dimer may be fine-tuned to exhibit either J-dimer characteristics at lower salt concentrations or H-dimer characteristics at high salt concentrations. FIG. 3C further shows that by altering both the temperature and salt concentrations, it is further possible to tune the chromophores for specific characteristics. FIG. 3D shows that not only the absorbance, but the emission is altered by changing the concentration of salt in the solution” [0067] (this is viewed to be inclusive of claims 9 and 17, wherein the excited state lifetime of the adjacent chromophores is altered by a change in solvent polarity, because polarity (dielectric constant) decreases with increasing salt concentration due to ion-induced structural changes in water). Yurke et al. does not teach encapsulation of the DNA-assembly. Mikkila et al. teaches DNA origami structures can be programmed into arbitrary shapes with nanometer scale precision, which opens up numerous attractive opportunities to engineer novel functional materials. One intriguing possibility is to use DNA origamis for fully tunable, targeted, and triggered drug delivery (abstract). Mikkila et al. teaches “The structural versatility and biocompatibility of DNA origami nanostructures open up opportunities for effective, tunable and targeted transport of molecules into cells. In principle, a single DNA origami structure could facilitate all functions necessary for drug delivery or docking molecules inside cells because its configuration can be changed and the structure may include both cell-targeting ligands and spatially organized drug molecules or functionalized sites. Recently, cellular transfection of origamis and DNA nanoassemblies containing drugs such as DNA intercalator doxorubicin has been demonstrated (page 2196). Mikkila et al. teaches how DNA origamis can be coated with virus capsid proteins (CP) in order to facilitate efficient cell transfection (see Figure 1). They observed that the DNA template surface was completely covered with the CPs resulting in the encapsulation of the origamis (page 2199. Col. 1 first para). They have shown that DNA origami structures can interact with virus capsid proteins in a controllable way to form new nanostructures and that coating of origamis by these proteins can be exploited to significantly enhance delivery of DNA origamis into human cells. Interestingly, transfection efficiency could be gradually raised with increasing CP concentrations up to a level at which DNA origamis were completely covered by the capsid proteins (page 2199, col. 2). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to encapsulate the DNA-assembly of Yurke using the method of Mikkila. Because Mikkila teaches that “ the obtained results conceivably make this self assembly-based method an excellent starting point for the development of diverse biomedical applications. The complete encapsulation gives a possibility to deliver multiple functionalized DNA origamis (this is viewed as the molecule of interest of claim 7) into cells and, in this way, use programmable combinations of specific drugs for attainable treatment procedures. In the future, organization of reactions inside the cell could be realized using modular docking sites on the origami, similarly as earlier demonstrated for RNA-based assemblies. (Mikkila page 2199, col. 2) Claim 13 is also rejected, because said claim does not further limit that the nucleic acid assembly of claim 12 is encapsulated in an inorganic material. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEZIA RILEY whose telephone number is (571)272-0786. The examiner can normally be reached 7:30-6:00pm. 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, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /JEZIA RILEY/ Primary Examiner, Art Unit 1681 11 May 2026
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Prosecution Timeline

Oct 31, 2022
Application Filed
May 13, 2026
Non-Final Rejection mailed — §102, §103, §112 (current)

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Prosecution Projections

1-2
Expected OA Rounds
83%
Grant Probability
90%
With Interview (+6.9%)
2y 5m (~0m remaining)
Median Time to Grant
Low
PTA Risk
Based on 1304 resolved cases by this examiner. Grant probability derived from career allowance rate.

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