Prosecution Insights
Last updated: April 19, 2026
Application No. 16/849,549

METHODS AND COMPOSITIONS FOR BIOSENSING

Final Rejection §103§112
Filed
Apr 15, 2020
Examiner
LU, FRANK WEI MIN
Art Unit
1683
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The University of North Carolina at Charlotte
OA Round
6 (Final)
63%
Grant Probability
Moderate
7-8
OA Rounds
4y 2m
To Grant
99%
With Interview

Examiner Intelligence

Grants 63% of resolved cases
63%
Career Allow Rate
430 granted / 684 resolved
+2.9% vs TC avg
Strong +67% interview lift
Without
With
+67.3%
Interview Lift
resolved cases with interview
Typical timeline
4y 2m
Avg Prosecution
70 currently pending
Career history
754
Total Applications
across all art units

Statute-Specific Performance

§101
1.6%
-38.4% vs TC avg
§103
24.8%
-15.2% vs TC avg
§102
14.3%
-25.7% vs TC avg
§112
49.5%
+9.5% vs TC avg
Black line = Tech Center average estimate • Based on career data from 684 resolved cases

Office Action

§103 §112
DETAILED ACTION Response to Amendment Applicant’s response to the office action filed on December 29, 2025 has been entered. The claims pending in this application are claims 1, 3, 4, 6, 7, 9, 10, and 12-21 wherein claims 7, 13, and 17 have been withdrawn in the office action mailed on August 9, 2022. The rejection not reiterated from the previous office action is hereby withdrawn in view of applicant’s amendment filed on December 29, 2025. Claims 1, 3, 4, 6, 9, 10, 12, 14-16, and 18-21 will be examined. Claim Objections Claim 21 is objected to because of the following informality: the phrase “wherein the colloidal quantum dots, in the non-aggregated state, include one or more first coupling moieties on their exterior surfaces” should be deleted since claim 1 has this phrase. 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. Claim 21 is 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 21 is rejected as vague and indefinite because it is unclear that a double-stranded nucleic acid consisting of a single-stranded guard nucleic acid bound to a single-stranded anti-guard nucleic acid from the analyte binding nucleic acid and a double-stranded nucleic acid consisting of a single-stranded guard nucleic acid bound to a single-stranded anti-guard nucleic acid from the coupling species are identical or not. Please clarify. 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. Claims 1, 6, 9, 12, 14-16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell et al., (J. Am. Chem. Soc., 121, 8122-8123, 1999) in view of Chan et al., (Science, 281, 2016-2018, 1998) and Anderson et al., (ACS Nano, 2, 1341-1352, 2008). Regarding claims 1, 6, 9, 12, 16, and 19, since the specification shows that “a luminescent species that ‘exhibits luminescence blinking’ in a non-aggregated state is to be understood to exhibit binary blinking, in which the individual luminescent species has alternating ‘on’ times (or ‘on’ states) and ‘off’ times (or ‘off’ states). As understood by one of ordinary skill in the art, such ‘on’ times (or ‘on’ states) correspond to times (or states) in which the luminescent species emits luminescence (e.g., fluorescence) when appropriately excited (e.g., by a beam of electromagnetic radiation having a wavelength corresponding to an excitation or absorption wavelength of the luminescent species). Similarly, ‘off’ times (or ‘off’ states) correspond to times (or states) in which the luminescent species does not emit luminescence (e.g., fluorescence), even when the luminescent species is appropriately excited (e.g., by the same excitation beam described above)”, “a luminescent species in an ‘aggregated state’ is not in a ‘non-aggregated state’ as described above” and “a luminescent species that ‘does not exhibit luminescence blinking’ in an aggregated state does not exhibit binary blinking, in the aggregate. In other words, individual luminescent species may (and generally do) continue to exhibit binary blinking behavior even when aggregated with other individual luminescent species. But the aggregate itself does not exhibit such blinking behavior, particularly not for aggregates of at least 3, at least 4, or at least 5 individual luminescent species. Instead, the composite or aggregate luminescence profile of the luminescent species ‘in the aggregated state’ exhibits non-blinking or quasi-continuous luminescence. That is, the composite or aggregate luminescence profile does not exhibit a binary pattern of alternating ‘on’ times (or ‘on’ states) and ‘off’ times (or ‘off’ states)” (see paragraphs [0030] to [0032] of US 2020/0240992 A1, which is US publication of this instant application), above teachings in the specification clearly indicate that colloidal quantum dots in a non-aggregated state exhibits luminescent blinking while colloidal quantum dots in an aggregated state do not exhibit luminescent blinking. Since Chan et al., teach that their quantum dots exhibit luminescence blinking in their non-aggregation state and do not exhibit luminescence blinking in their aggregation state (see pages 2017 and 2018), the quantum dots taught by both Mitchell et al., and Chan et al., are made by the same material, CdSe/ZnS (see page 8122 from Mitchell et al., and page 2016 from Chan et al.,), Mitchell et al., in view of Chan et al., teach a sensing composition, the composition comprising: a population of individual luminescent species (ie., highly luminescent semiconductor quantum dots (eg., cadmium selenide)) wherein the luminescent species, in a non-aggregated state (ie., highly luminescent semiconductor quantum dot-3’-propylthiol-terminated 22 mer DNA in the absence of a complementary “linker” DNA and 5’-hexylthiol-termiated 22 mer DNA), exhibits luminescence blinking and, in an aggregated state (ie., an aggregated complex formed by highly luminescent semiconductor quantum dot-3’-propylthiol-terminated 22 mer DNA, a complementary “linker” DNA and 5’-hexylthiol-termiated 22 mer DNA in the presence of the complementary “linker” DNA), do not exhibit luminescence blinking; and wherein the individual luminescent species are operable to transition from the non-aggregated state to the aggregated state in the presence of an analyte (ie., the complementary “linker” DNA) and an analyte binding species (ie., 3’-propylthiol-terminated 22 mer DNA or 5’-hexylthiol-termiated 22 mer DNA), wherein the analyte binding species, in the presence of the analyte, binds to the analyte and forms a coupling species (ie., 3’-propylthiol-terminated 22 mer DNA- complementary “linker” DNA-5’-hexylthiol-termiated 22 mer DNA), wherein the coupling species is operable to couple a plurality of the luminescent species to one another, wherein the individual luminescent species comprise colloidal quantum dots, wherein the colloidal quantum dots, in the non-aggregated state, include one or more first coupling moieties (ie., 22 mer DNA) on their exterior surfaces; the colloidal quantum dots comprise a ligand shell (ie., a mercaptopropionic acid shell), the analyte binding species comprises an analyte binding nucleic acid, and the analyte comprises an analyte nucleic acid as recited in claim 1 wherein ligands (ie., mercaptopropionic acids) of the ligand shell are bonded to surfaces of the quantum dots via covalent bonds (ie., S-C covalent bond) as recited in claim 6, the colloidal quantum dots comprise one or more surface binding sites operable to interact with the coupling species (ie., 3’-propylthiol-terminated 22 mer DNA-complementary “linker” DNA-5’-hexylthiol-termiated 22 mer DNA) as recited in claim 9, the quantum dots are formed by a Group II-VI semiconductor material (eg., CdSe) as recited in claim 12, the quantum dots have a core/shell architecture as recited in claim 16, and the quantum dots have an emission in the range of 350 nm to 650 nm as recited in claim 19 (see pages 8122 and 8123, Scheme 1 and Figure 1). Regarding claims 14 and 15, Mitchell et al., teach that the quantum dots further comprise a metal dopant (ie., ZnS) as recited in claim 14 (see Scheme 1). Since it is known that “[D]uring exposure to long wavelength (366 nm) UV light, the zinc sulfide is found to fluoresce and phosphoresce with impressive intensity and vibrant color. After turning the UV light ‘off’, we see the evidence of phosphorescence emission from the zinc sulfide in the form of an ‘eerie green’ glow. The glow is maintain for several seconds” (see properties of “ZnS”), Mitchell et al., disclose that the metal dopant (ie., ZnS) is light emitting as recited in claim 15. Mitchell et al., and Chan et al., do not disclose that ligands of the ligand shell include 4 to 50 carbon atoms as recited in claim 1. Anderson et al., teach amphiphilic polymer-coated TOPO/HAD-stabilized ZnS-capped CdSe QDs (see pages 1344 and 1350, and Figures 1 and 2). Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the sensing composition recited in claim 1 wherein ligands (ie., the amphiphilic polymer synthesized in Figure 1 of Anderson et al.,) of the ligand shell include 4 to 50 carbon atoms in view of the prior arts of Mitchell et al., Chan et al., and Anderson et al.. One having ordinary skill in the art would have been motivated to do so because Anderson et al., teach amphiphilic polymer-coated TOPO/HAD-stabilized ZnS-capped CdSe QDs (see pages 1344 and 1350, and Figures 1 and 2) and the simple substitution of one kind of quantum dot (eg., the quantum dots having mercaptopropionic acids as ligands taught by Mitchell et al.,) from another kind of quantum dot (eg., the amphiphilic polymer-coated TOPO/HAD-stabilized ZnS-capped CdSe QDs taught by Anderson et al., wherein the amphiphilic polymer synthesized in Figure 1 of Anderson et al., are ligands) during the process of making the luminescent species in the sensing composition recited in claim 1, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the quantum dots having mercaptopropionic acids taught by Mitchell et al., and the amphiphilic polymer-coated TOPO/HAD-stabilized ZnS-capped CdSe QDs taught by Anderson et al., are used for the same purpose (ie., making the luminescent species in the luminescent species in the sensing composition recited in claim 1) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the luminescent species in the sensing composition recited in claim 1 by substituting of the quantum dots having mercaptopropionic acids taught by Mitchell et al., from the amphiphilic polymer-coated TOPO/HAD-stabilized ZnS-capped CdSe QDs taught by Anderson et al., in view of the prior arts of Mitchell et al., Chan et al., and Anderson et al., such that ligands (ie., the amphiphilic polymer synthesized in Figure 1 of Anderson et al.,) of the ligand shell recited in claim 1 would include 4 to 50 carbon atoms. Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09. Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955). Response to Arguments In page 7, third paragraph bridging to page 9, third paragraph of applicant’ remarks, applicant argues that: (1) in view of the office action mailed on August 27, 2025, “[A]pplicant submits that Mitchell et al. fails to teach a population of individual luminescent species wherein the luminescent species in a non-aggregated state exhibits luminescence blinking, as alleged by the Office. The Office was not persuaded by Applicant’s prior remarks that Mitchell et al. and Chan et al. failed to disclose all of the limitations of claim 1 because, in the eyes of the Office, ‘the quantum dots taught by both Mitchell et al. and Chan et al. are made by the same material, CdSe/ZnS ….’ Accordingly, because the quantum dots of Chan et al. exhibit luminescence blinking in their non-aggregation state and do not exhibit luminescence blinking in their aggregation state, ‘the quantum dots taught by Mitchell et al., must have an ability to exhibit luminescence blinking in their non-aggregation state and not exhibit luminescence blinking in their aggregation state’’, “[J]ust because two materials are made of the same basic elements does not necessitate that identical behaviors will follow. Further, deviations in how the materials are prepared or the physical surroundings of the materials may lead to differing behaviors. This is especially poignant here, because the CdSe/ZnS QDs of Mitchell et al. and Chan et al. are not prepared in the same manner. As an initial matter, physical parameters such as pressure, temperature, and electric and magnetic fields modify the photoluminescence of CdSe quantum dots, proving the basic notion that just because they have the same basic elements does not mean their photoluminescent properties are identical”, “there are various chemical methods to modify QD luminescence. For example, a recent study observed both ‘photoluminescence enhancement and near-complete blinking suppression for QDs either embedded in polymer containing dithiothreitol or supplemented with β-mercaptoethanol. In both cases, the thiol moieties act as electron donors, which suppress non-radiative carrier recombination in defects” as evidence by Shibu et al., “Photoluminescence of CdSe and CdSe/ZnS quantum dots: Modifications for making the invisible visible at ensemble and single-molecule levels” Coordination Chemistry Reviews, 263-264, 2-12, 2014, “the addition of thiol-containing compounds to CdSe/ZnS QDs has been known to have unanticipated effects on QDs, ranging from enhancement of photoluminescence to entirely removing the blinking behavior of QDs, even though the base elements are the same (i.e., CdSe core and ZnS cap). In Mitchell et al., 3-mercaptopropionic acid-a thiol-containing compound- was used to passivate the QD surface”, “[I]n Chan et al., mercaptoacetic acid was used for solubilization of the QDs”, “the QDs in Mitchell et al. and Chan et al. were treated with different thiol-containing compounds, which have been observed to affect the luminescent behaviors of QDs in unique and unpredictable ways. Accordingly, the Office's proposition that the QDs of Mitchell et al. must exhibit the same blinking pattern as the QDs of Chan et al. because they are both made of a CdSe core and ZnS cap is not necessarily true-the photoluminescence of a QD is dictated by many factors, but of particular importance here, the addition of a thiol-containing compound can eliminate the blinking behavior of a QD altogether. Mitchell et al. never discloses, nor even references, blinking behavior, only a decrease in fluorescence. Thus, it cannot be said that Mitchell et al. teaches a population of individual luminescent species wherein the luminescent species in a non-aggregated state exhibit luminescent blinking just due to its similarities to Chan et al., especially without considering the diverging preparation protocol of the QDs. Further, as admitted by the Office, both Mitchell et al. and Chan et al. fail to disclose that ligands of the ligand shell include 4 to 50 carbon atoms as recited in claim 1. The Office remedies this by stating that ‘Anderson et al., teach amphiphilic polymer-coated TOPO/HAD-stabilized ZnS-capped CdSe QDs.’ Regardless, Anderson et al. does not cure the deficiencies of Mitchell et al. and Chan et al. established above-all of the limitations of claim 1 are still not disclosed. In view of the above, Applicant respectfully submits that the combination of Mitchell et al., Chan et al., and Anderson et al. does not destroy the patentability of independent claim 1 as amended. Moreover, claims 6, 9, 12, 14-16, and 19 add additional patentable subject matter to their base claim and are therefore also novel over the combination of Mitchell et al., Chan et al., and Anderson et al. based at least on their dependency therefrom”. These arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection. Although applicant argues that “[J]ust because two materials are made of the same basic elements does not necessitate that identical behaviors will follow. Further, deviations in how the materials are prepared or the physical surroundings of the materials may lead to differing behaviors. This is especially poignant here, because the CdSe/ZnS QDs of Mitchell et al. and Chan et al. are not prepared in the same manner. As an initial matter, physical parameters such as pressure, temperature, and electric and magnetic fields modify the photoluminescence of CdSe quantum dots, proving the basic notion that just because they have the same basic elements does not mean their photoluminescent properties are identical”, applicant has no evidence to show that the luminescent species taught by Mitchell et al., in a non-aggregated state (ie., highly luminescent semiconductor quantum dot-3’-propylthiol-terminated 22 mer DNA in the absence of a complementary “linker” DNA and 5’-hexylthiol-termiated 22 mer DNA) cannot exhibit luminescence. Since it is known that Fluorescence intermittency or blinking is the phenomenon of random switching between ON (bright) and OFF (dark) states of the emitter under its continuous excitation and is a common property of the nanoscale emitters (molecular fluorophores, colloidal quantum dots such as CdSe-ZnS core-shell nanocrystals) related to the competition between the radiative and non-radiative relaxation pathways (see “Fluorescence intermittency” from Wikipedia), the CdSe/ZnS colloid quantum dots taught by Mitchell et al., have an ability to exhibit luminescent blinking in their non-aggregation state. Since Chan et al., teach that their quantum dots exhibit luminescence blinking in their non-aggregation state and do not exhibit luminescence blinking in their aggregation state (see pages 2017 and 2018), the quantum dots taught by both Mitchell et al., and Chan et al., are made by the same material, CdSe/ZnS (see page 8122 from Mitchell et al., and page 2016 from Chan et al.,), which should have the same function, the quantum dots taught by Mitchell et al., must have an ability to exhibit luminescence blinking in their non-aggregation state and not exhibit luminescence blinking in their aggregation state. Furthermore, although Shibu et al., teach that blinking of QDs can be suppressed using thiols such as dithiothreotol (DTT) or supplemental with β-mercaptoethanol and both mercaptopropionic acid taught by Mitchell et al., and mercaptoacetic acid taught by Chan et al., have thiols, applicant has no evidence to show that the luminescent species taught by Mitchell et al., in a non-aggregated state (ie., highly luminescent semiconductor quantum dot-3’-propylthiol-terminated 22 mer DNA in the absence of a complementary “linker” DNA and 5’-hexylthiol-termiated 22 mer DNA) cannot exhibit luminescence and applicant’s argument “the QDs in Mitchell et al. and Chan et al. were treated with different thiol-containing compounds, which have been observed to affect the luminescent behaviors of QDs in unique and unpredictable ways” is incorrect. In addition, Anderson et al., is used for combine with Mitchell et al., and Chan et al., to reject claim 1. Claims 3, 4, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell et al., in view of Chan et al., and Anderson et al., as applied to claims 1, 6, 9, 12, 14-16, and 19 above. The teaching Mitchell et al., Chan et al., and Anderson et al., have been summarized previously, supra. Mitchell et al., and Anderson et al., do not disclose that the colloidal quantum dots exhibit a size distribution having a standard deviation of 5-15 percent as recited in claim 3, the colloidal quantum dots exhibit a size distribution having a standard deviation of 5-10 percent as recited in claim 4, and the quantum dots have a quantum yield of 30-50 percent as recited in claim 20. However, the quantum dots taught by Mitchell et al., is highly luminescent CdSe/ZnS QDs (see page 8122). Chan et al., teach that their CdSe/ZnS QDs are strongly luminescent having 35% to 50% quantum yield and are not homogeneous in size with about 5% variation (see page 2016, right column and page 2017, middle column). Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the sensing composition recited in claims 3, 4, and 20 wherein the colloidal quantum dots exhibit a size distribution having a standard deviation of 5-15 percent and the quantum dots have a quantum yield of 30-50 percent in view of the prior arts of Mitchell et al., Chan et al., and Anderson et al.. One having ordinary skill in the art would have been motivated to do so because the quantum dots taught by Mitchell et al., is highly luminescent CdSe/ZnS QDs (see page 8122) while CdSe/ZnS QDs taught by Chan et al., are strongly luminescent having 35% to 50% quantum yield and are not homogeneous in size with about 5% variation (see page 2016, right column and page 2017, middle column), and the simple substitution of one kind of quantum dot (ie., the CdSe/ZnS QDs taught by Anderson et al.,) from another kind of quantum dots (ie., the CdSe/ZnS QDs taught by Chan et al.,) during the process of making the quantum dots as recited in claims 3, 4, and 20, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the CdSe/ZnS QDs taught by Anderson et al., and the CdSe/ZnS QDs taught by Chan et al., are used for the same purpose (ie., making the quantum dots recited in claim 1) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the quantum dots recited in claims 3, 4, and 20 by substituting the CdSe/ZnS QDs taught by Anderson et al., from the CdSe/ZnS QDs taught by Chan et al., in view of the prior arts of Mitchell et al., Chan et al., and Anderson et al., such that the colloidal quantum dots would exhibit a size distribution having a standard deviation of 5-15 percent and have a quantum yield of 30-50 percent. Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09. Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955). Response to Arguments In page 9, fourth to last paragraphs of applicant’ remarks, applicant argues that “the limitations of claim 1 are not disclosed by Mitchell, Anderson, and Chan. Further, a person of ordinary skill would not modify the quantum dots of Mitchell according to Chan to create blinking behavior, as Chan finds the blinking to be a ‘problem’ in ultrasensitive detection applications. See Chan at 2017. Thus, Chan does not cure the deficiencies of Mitchell and Anderson. As such, the alleged combination fails to disclose each limitation of claim 1.Applicant submits that claims 3, 4, and 20 depend either directly or indirectly from claim 1 and include all limitations of claim 1”. These arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection because a combination of Mitchell et al., Chan et al., and Anderson et al., teach all limitation recited in claim 1 (see above Response to Arguments related to Rejection Item No. 7). Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Mitchell et al., in view of Chan et al., and Anderson et al., as applied to claims 1, 6, 9, 12, 14-16, and 19 above, and further in view of Wu et al., (Nature, 21, 41-46, 2003). The teaching Mitchell et al., Chan et al., and Anderson et al., have been summarized previously, supra. Mitchell et al., Chan et al., and Anderson et al., do not disclose that the binding sites comprises streptavidin as recited in claim 10. Wu et al., teach to make streptavidin conjugated and amphiphilic polymer-coated CdSe/ZnS quantum dots by coupling streptavidin to the amphiphilic polymer-coated CdSe/ZnS quantum dots by an EDC-medicated coupling reaction (see page 45, left column). Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the sensing composition recited in claim 10 wherein the binding sites comprises streptavidin in view of the prior arts of Mitchell et al., Anderson et al., Chan et al., and Wu et al.. One having ordinary skill in the art would have been motivated to do so because Wu et al., have successfully made streptavidin conjugated and amphiphilic polymer-coated CdSe/ZnS quantum dots by coupling streptavidin to the amphiphilic polymer-coated CdSe/ZnS quantum dots by an EDC-medicated coupling reaction (see page 45, left column). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the colloidal quantum dots having binding sites comprising streptavidin recited in claim 10 by coupling streptavidin to the amphiphilic polymer-coated TOPO/HAD-stabilized ZnS-capped CdSe QDs taught by Anderson et al., in view of the prior arts of Mitchell et al., Chan et al., Anderson et al., and Wu et al., such that the colloidal quantum dots recited in claim 10 have an ability to bind to a biotin-labeled target or probe. Response to Arguments In page 10, first to third paragraphs of applicant’ remarks, applicant argues that “[A]s stated above, the combination of Mitchell et al., Chan et al., and Anderson et al. does not destroy the patentability of independent claim 1 as amended. Wu et al. fails to cure the deficiencies of the combination of Mitchell et al., Chan et al., and Anderson et al. Therefore, the combination of Mitchell et al., Chan et al., Anderson et al., and Wu et al. also fails to render obvious claim 1. Moreover, whereas claim 10 depends from and further limits claim 1, the combination of Mitchell et al., Chan et al., Anderson et al., and Wu et al. fails to render obvious this claim as well for at least this reason”. These arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection because a combination of Mitchell et al., Chan et al., and Anderson et al., teach all limitation recited in claim 1 (see above Response to Arguments related to Rejection Item No. 7). Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Mitchell et al., in view of Chan et al., and Kim et al., (J. Am. Chem. Soc., 125, 11466-11467, 2003). The teaching of Mitchell et al., and Chan et al., have been summarized previously, supra. Mitchell et al., and Chan et al., disclose all limitations recited in claim 18 (see above rejection under 35 U.S.C. 103 for claim 1 which shares a lot of limitations of claim 18) except that the quantum dots have a Type II electronic structure as recited in claim 18. Kim et al., teach type-II colloidal QDs such as CdTe/CdSe(c/s) QDs (CdTe/CdSe QDs) or CdSe/ZnTe(c/s) QDs (CdSe/ZnTe QDs) and some advantages of type-II colloidal QDs “[T]ype-II structures can allow access to wavelengths that would otherwise not be available with a single material. In addition, the separation of charges in the lowest excited states of type-II nanocrystals should make these materials more suitable in photovoltaic or photoconduction applications, where the QDs are the chromophores and one of the photocarriers is injected from the QD into a matrix before recombination can occur” (see page 11466). Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the sensing composition recited in claim 18 wherein the quantum dots have a Type II electronic structure in view of the prior arts of Mitchell et al., Chan et al., and Kim et al.. One having ordinary skill in the art would have been motivated to do so because Kim et al., teach type-II colloidal QDs such as CdTe/CdSe(c/s) QDs (CdTe/CdSe QDs) and CdSe/ZnTe(c/s) QDs (CdSe/ZnTe QDs) and some advantages of type-II colloidal QDs “[T]ype-II structures can allow access to wavelengths that would otherwise not be available with a single material. In addition, the separation of charges in the lowest excited states of type-II nanocrystals should make these materials more suitable in photovoltaic or photoconduction applications, where the QDs are the chromophores and one of the photocarriers is injected from the QD into a matrix before recombination can occur” (see page 11466) and the simple substitution of one kind of QDs (eg., CdSe/ZnS QDs taught by Mitchell et al.,) from another kind of QDs (eg., the quantum dots having a Type II electronic structure such as such as CdTe/CdSe QDs or CdSe/ZnTe QDs taught by Kim et al.,) during the process of making the luminescent species in the sensing composition recited in claim 18, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the QDs taught by Mitchell et al., and the QDs taught by Kim et al., are used for the same purpose (ie., making the luminescent species in the sensing composition recited in claim 1) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the luminescent species in the sensing composition recited in claim 18 by substituting of the QDs taught Mitchell et al., from the QDs taught by Kim et al., in view of the prior arts of Mitchell et al., Chan et al., and Kim et al., in order to take above advantages of the quantum dots having a Type II electronic structure. Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09. Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955). Response to Arguments In page 10, fourth to last paragraphs of applicant’ remarks, applicant argues that “[A]pplicant submits that each and every element of at least claim 18 is not disclosed by the combination of Mitchell et al. in view of Chan et al. and Kim et al. As stated above for claim 1, Mitchell et al. in view of Chan et al. does not teach or suggest a population of individual luminescent species wherein the luminescent species in a non-aggregated state exhibits luminescence blinking. Moreover, Kim et al. does not cure this deficiency in Mitchell et al.”. These arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection because a combination of Mitchell et al., and Chan et al., teach all limitation recited in claim 18 except that the quantum dots have a Type II electronic structure which is taught by Kim et al., (see above Response to Arguments related to Rejection Item No. 7). Conclusion 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. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph. D., whose telephone number is (571)272-0746. The examiner can normally be reached Monday to Friday, 9 AM to 5 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, Anne Gussow, Ph.D., can be reached at 571-272-6047. 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. /FRANK W LU/ Primary Examiner, Art Unit 1683 March 19, 2026
Read full office action

Prosecution Timeline

Apr 15, 2020
Application Filed
Dec 28, 2022
Non-Final Rejection — §103, §112
Apr 03, 2023
Response Filed
Jun 03, 2023
Final Rejection — §103, §112
Sep 21, 2023
Response after Non-Final Action
Dec 08, 2023
Request for Continued Examination
Dec 11, 2023
Response after Non-Final Action
Apr 26, 2024
Non-Final Rejection — §103, §112
Oct 01, 2024
Response Filed
Nov 23, 2024
Final Rejection — §103, §112
May 27, 2025
Request for Continued Examination
May 29, 2025
Response after Non-Final Action
Aug 23, 2025
Non-Final Rejection — §103, §112
Dec 29, 2025
Response Filed
Mar 20, 2026
Final Rejection — §103, §112 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

7-8
Expected OA Rounds
63%
Grant Probability
99%
With Interview (+67.3%)
4y 2m
Median Time to Grant
High
PTA Risk
Based on 684 resolved cases by this examiner. Grant probability derived from career allow rate.

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