DETAILED ACTION
Notice of Pre-AIA or AIA Status and New Examiner
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Please note that the examiner for this application has changed. Please address future correspondence to Robert T. Crow (Art Unit 1683) whose telephone number is (571) 272-1113.
Continued Examination Under 37 CFR 1.114
3. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5 December 2025 has been entered.
Amendments and Status of the Claims
4. This action is in response to papers filed 5 December 2025 in which no claims were amended and claims 27-34 were canceled.
5. It is noted that the after-final claims filed 29 September 2025 included new claims 35 and 36, which, as noted in the Advisory Action mailed 7 October 2025, were not entered. Because the papers filed 5 December 2025 list claims 35-36 and “Not Entered” and contain no text were not entered, clams 35-36 are cancelled.
6. The previous requirement for species election is withdrawn
7. All previous objections and/or rejections not reiterated below are withdrawn.
8. Claims 1-26 are under prosecution.
Claim Interpretation
9. The claims are drawn to a “system.” The specification recites a “system” wherein the “system” is defined in terms of structural limitations. In addition, the claims recite structural limitations of the “system.” Thus, the “system” is interpreted to encompass any collection of reagents and parts used together that are not necessarily part of a completely integrated single unitary device. Any further interpretation of the word is considered an “intended use” and does not impart any further structural limitation on the claimed subject matter.
10. The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
11. This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitations is/are:
A. A “first detector configured to…,” a ”second detector configured to…,” and a “processor configured to…” in claim 1;
B. A “processor configured to…” in claim 2; and
C. A “light source…configured to…” in claim 17
However, these claim limitations are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, as there is no corresponding limiting structure described in the specification as performing the claimed function, and equivalents thereof.
If Applicant does intend to have these limitations interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, Applicant should present a sufficient showing that the specification recites sufficient limiting structure to perform the claimed function so as to clarify proper interpretation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
12. 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.
13. Claims 2-12, 17, 20, and 22-26 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.
A.I. Claims 2 (upon which claims 3-12, 17, 20, and 22-26 depend), 3, and 4 are each indefinite in the recitation “the fluorescent labels,” which lacks antecedent basis in the previous recitation of “a single fluorescent label,” “ a first fluorescent label,” “a second fluorescent label,” etc.
A.II. In addition, with respect to claim 3, it is unclear if the all of the labels are required to be from one genus (e.g., polymethine derivatives).
For the purposes of examination, claim 3 is interpreted as requiring at least one label from the recited group.
A.III. Further, with respect to claim 4, it is unclear if the entire group of labels is required.
For the purposes of examination, claim 4 is interpreted as requiring only one of the claimed labels.
B.I. Claim 23 is indefinite in the recitation “the nucleotide analogs,” which lacks antecedent basis in the previous recitation of “a first nucleotide analog,” “ a second nucleotide analog,” etc.
B.II. In addition, it is unclear if the entire group of analog is required.
For the purposes of examination, claim 4 is interpreted as requiring only one of the claimed labels.
Claim Rejections - 35 USC § 103
14. 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.
15. 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.
16. Claims 1-2, 12, 18-21, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Ang et al. (U.S. Patent Application Publication No. US 2018/0217170 A1, published 2 August 2018) and Short (U.S. Patent Application Publication No. US 2003/0219752 A1, published 27 November 2003).
Regarding claim 1, Ang et al. teach a system (paragraph 0038) comprising a substrate, in the form of a nucleic acid array (paragraph 0078), as well as an excitation source and a detector (paragraphs 0006-0007), wherein the light source is a laser (paragraph 0126). Ang et al. also teach the array comprises a template nucleic acid template bound (i.e., present) on the array and hybridized to a primer, which has been extended with a tagged nucleotide (paragraphs 0169-0170). Ang et al. further teach one nucleotide is labeled with a label detected in two different channels of a detector (paragraphs 0173-0174), and that the systems have the added advantage of reducing the cost of sequencing (paragraph 0005). Thus, Ang et al. teach the known techniques discussed above
It is noted that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments (see MPEP § 2123). Thus, the teaching of Ang et al. that the system includes no more than a single detector (i.e., microfluorometer; paragraph 0007) “[i]n some aspects” encompasses the alternate embodiment wherein there is more than one detector (see also paragraph 0121).
While Ang et al. teach different colors are detected in different channels, including a single label detected in two different channels (paragraph 0173), Ang et al. do not teach two different detectors or a processor.
However, Short teaches nucleic acid sequencing (paragraph 0100) comprising a plurality of separate detectors, wherein each detector resolves emissions at a single wavelength (paragraph 575). Short further teaches computerized determination of sequences (paragraph 0418) and that the computer carries out the methods described therein (paragraph 0523), which includes providing fluorescence excitation via a laser (paragraph 0574). Short also teach the advantage of suppressing background fluorescence activity (paragraph 0579). Thus, Short teaches the known techniques discussed above.
It is also noted that the courts have held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art (In re Venner, 262 F.2d 91, 95, 120 USPQ 193, 194 (CCPA 1958)), See MPEP 2144.04 III.
Thus, providing a process that executes instructions taught by the cited prior art is obvious.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of the cited prior art to arrive at the instantly claimed system with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a system having the added advantages of reducing the cost of sequencing as explicitly taught by Ang et al. (paragraph 0005) and suppressing background fluorescence activity as explicitly taught by Short (paragraph 0579). In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with predictable results because the known techniques of the cited prior art predictably result in systems useful for detecting different colors/wavelength and nucleic acid analysis.
Regarding claim 2, the system of claim 1 is discussed above. Ang et al. teach the claimed labeling scheme (paragraph 0172), as well as generating light to excite the labels and detect the emissions in claimed arrangement in channels (paragraph 0172-0173), which, in view of Short, occurs in the different detectors. Ang et al. also teach nucleotide analogs as well as four different nucleotides (paragraphs 0170-0171); thus, it would have been obvious the have four nucleotide analogs for each of the bases.
It is reiterated that the courts have held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art
Thus, providing a process that executes claimed instructions taught by the cited prior art is obvious.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
Regarding claim 12, the system of claim 2 is discussed above. It is noted that the claim does not prohibit the nucleotide analog having the “single fluorescent label” of claim 1 from being the same nucleotide and label as one of the nucleotide analogs having a fluorescent label in claim 2. This, because the first fluorescent label of claim 2 can be the same as the single fluorescent label of claim 1, the first fluorescent label would be detectable by both detectors.
Regarding claim 18, the system of claim 1 is discussed above. Ang et al. also teach CMOS image sensors (paragraph 0025).
Regarding claim 19, the system of claim 1 is discussed above. Ang et al. also teach optical (i.e., excitation) filters image sensors (paragraph 0126).
Regarding claim 20, the system of claim 2 is discussed above. Ang et al. also teach polymerase (paragraph 0169).
Regarding claim 21, the system of claim 1 is discussed above. Ang et al. also teach the substrate (i.e., array) comprises a plurality of cavities (i.e., wells; paragraph 0116).
Regarding claims 23-25, the system of claim 2 is discussed above. Ang et al. also teach the nucleotide analogs are reversibly blocked (paragraph 0170), and include rbATP, rbCTP, rbGTP, and rbTTP (paragraph 0173).
17. Claims 3-7 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Ang et al. (U.S. Patent Application Publication No. US 2018/0217170 A1, published 2 August 2018) and Short (U.S. Patent Application Publication No. US 2003/0219752 A1, published 27 November 2003) as applied to claims 2 and 24 above, and further in view of Romanov (PCR International Application Publication No. WO 2018/060482 A1, published 5 April 2018).
Regarding claims 3-7 and 26, the systems of claim 2 and 24 are discussed above in Section 16.
None of the previously cited prior art teaches the claimed labels.
However, Romanov teaches benzopyran dyes (i.e., claim 3) as labels for nucleic acid sequencing (paragraph 0009), including formula I-11, differs only from one of the compounds of claim 4 by substitution of the claimed H on that amide nitrogen for the group CH2CH2CH2SO3H (see also compound I-10; which has an additional carbon on a nitrogen and forms an additional ring). Romanov also teaches an additional nucleotide analog with no label (i.e., claim 5, paragraph 0113), as well as the same base having two different compounds (i.e., claim 6; paragraph 0119).
In addition, the courts have stated:
similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close’ structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)).
The courts have also stated:
[c]ompounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious) (see MPEP 2144.09).
Therefore, the claimed compound is an obvious variant of the prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
With respect to claim 7, it is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed dimmer emission merely represent an obvious variant of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
Romanov further teaches the bases are modified (paragraph 0119) and comprise reversible 3’ terminator blocking groups (i.e., claim 26; paragraph 0109), and that the labels have the added advantage of improved sequencing reads (paragraph 0009). Thus, Romanov teaches the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Romanov with the previously cited prior art to arrive at the instantly claimed systems with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in systems having the added advantage of improved sequencing reads as explicitly taught by Romanov (paragraph 0009). In addition, it would have been obvious to the ordinary artisan that the known techniques of Romanov could have been combined with the previously cited prior art with predictable results because the known techniques of Romanov predictably result in systems useful for detecting different colors/wavelength and nucleic acid analysis.
18. Claims 10-11, 13-16, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Ang et al. (U.S. Patent Application Publication No. US 2018/0217170 A1, published 2 August 2018) and Short (U.S. Patent Application Publication No. US 2003/0219752 A1, published 27 November 2003) as applied to claims 1-2 above, and further in view of Langlois et al. (U.S. Patent Application Publication No. US 2020/0080142 A1, published 12 March 2020).
Regarding claims 10-11, 13-16, and 22, the systems of claims 1-2 are discussed above in Section 16.
While Ang et al. teach reversibly blocked analogs (i.e., paragraph 0173), neither Ang et al. nor Short teach the claimed cleavable linkers or Stokes shifts.
However, Langlois et al. teach nucleic acids sequencing systems (Abstract) comprising detectors (i.e., at least one, which encompasses two; paragraph 0004) and nucleotides that are each labeled with labels having different fluorescence emissions (paragraph 0005). Langlois et al. also teach the labels have Stokes shifts in the claimed ranges (i.e., claim 10; paragraph 0033), as well as emissions that do no overlap (paragraph 0027); thus, it would have been obvious for the detectors to have wavelength ranges that correspond to the labels neither of which overlap (i.e., claim 13), which results in a first fluorescent label is only detectable by the first detector, and a second label is only detectable by the second detector (i.e., claim 11).
Langlois et al. further teach the light source has an excitation wavelength range that varies from about 400 to 800 (paragraph 0027), and that the labels can emit anywhere between the same two ranges, including about 400/410 to 460 nm (i.e., claim 15; paragraph 0032), which includes lower ranges that that of the light source. Thus, it would have been obvious that the light source could have a range including at least one wavelength that is shorter than (i.e., claim 14) or longer than (i.e., claim 16) the ranges of label emissions.
It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
It is also reiterated that he courts have also found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
Langlois et al. also teach nucleotide analogs of A, T, G, and C linked to fluorescent labels with cleavable linkers (i.e., claim 22; paragraph 0045), and that the systems have the added advantage of allowing minimal to no cross-talk between the labels (paragraph 0016). Thus, Langlois et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Langlois et al. with the previously cited prior art to arrive at the instantly claimed systems with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in systems having the added advantage of allowing minimal to no crosstalk between the labels as explicitly taught by Langlois et al. (paragraph 0016). In addition, it would have been obvious to the ordinary artisan that the known techniques of Langlois et al. could have been combined with the previously cited prior art with predictable results because the known techniques of Langlois et al. predictably result in systems useful for detecting different colors/wavelength and nucleic acid analysis.
19. Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Ang et al. (U.S. Patent Application Publication No. US 2018/0217170 A1, published 2 August 2018) and Short (U.S. Patent Application Publication No. US 2003/0219752 A1, published 27 November 2003) as applied to claim 2 above, and further in view of Chang (U.S. Patent Application Publication No. US 2011/0130306 A1, published 2 June 2011).
Regarding claim 17, the system of claim 2 is discussed above in Section 16.
None of the previously cited prior art teaches two photon processes.
However, Chang teaches detection of nucleic acids (paragraph 0253) two-photon excitation light sources have the added advantage of reduced photodamage and minimized background absorption and scattering (paragraph 0278). Thus, Chang teaches the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Chang with the previously cited prior art to arrive at the instantly claimed system with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a system having the added advantage of reduced photodamage and minimized background absorption as explicitly taught by Chang (paragraph 0278). In addition, it would have been obvious to the ordinary artisan that the known techniques of Chang could have been combined with the previously cited prior art with predictable results because the known techniques of Chang predictably result in systems useful for detecting labeled nucleic acid analytes.
Response to Arguments
20. Applicant’s arguments, including those presented in the Declaration filed 5 December 2025, have been considered but are moot in view of the new rejections.
Conclusion
21. No claim is allowed.
22. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert T. Crow whose telephone number is (571)272-1113. The examiner can normally be reached M-F 8:00-4:30.
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Robert T. Crow
Primary Examiner
Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
Prosecution Insights