FINAL ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Amendments and Status of the Claims
2. This action is in response to papers filed 27 March 2026 in which the specification and claims 2, 4, 7, 15-16, 18, and 19-20 were amended, claims 6, 14, and 17 were canceled, and new claim 21 was added. All of the amendments have been thoroughly reviewed and entered.
Any previous rejections not reiterated below are withdrawn in view of the amendments and the Terminal Disclaimer discussed below.
Applicant’s arguments have been thoroughly reviewed and are addressed following the rejections necessitated by the amendments.
3. Claims 2-5, 7-13, 15-16, and 18-21 are under prosecution.
4. This Office Action includes new rejections necessitated by the amendments.
Terminal Disclaimer
5. The terminal disclaimer filed on 27 March 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patents 10,662,468, 11,001,879, 11,549,138, 11,761,030 and 12,391,980, and U.S. Patent Application Nos. 19/264,527, 18/516,576, 19/021,568, and 19/021,991
has been reviewed and is accepted. The terminal disclaimer has been recorded.
Interview Summary
6. The interview summary is acknowledged and the interview record is complete.
Information Disclosure Statement
7. The Information Disclosure Statement filed 27 March 2026 is acknowledged and has been considered.
Specification
8. The substitute specification filed 27 March 2026 has not been entered because it does not conform to 37 CFR 1.125(b) and (c) because: the marked up Specification is not properly labeled as such nor is the clean copy properly labeled.
Claim Rejections - 35 USC § 112
9. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
10. Claims 2-5, 7-13, 15-16, and 18-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a new matter rejection.
A. Claim 2 (upon which clams 3-20 depend) recites each of the following:
I. Generating a nucleic acid comprising at least a portion of the analyte sequence or a complement thereof and the location sequence or a complement thereof. The claim encompasses each feature having the first and second nucleic acids separate from one another in a capture area; thus amplification to include both sequences would be amplification to form a bridged structure between the two separate probes . A review of at least parent Application 15/187,667 (which is the oldest application in the continuity chain; henceforth the ‘598 patent) does not yield teachings of this embodiment.
II. Capture areas comprising a second sequence that identifies a location. A review of the ‘598 patent only yields teachings where the location probe is delivered to the substate after parent analytes/biological samples have been delivered (e.g., Figures 1 and 2), and does not support location sequences prior to fixing the sample to a support.
B. Claim 13 recites contacting a tissue section with capture areas. The ‘598 patent only teaches tissue section that themselves form an array (e.g., column 8, lines 30-45), but not teach oligonucleotide arrays contacted with tissue sections.
C. Claim 16 recites denaturation. While the ‘598 Patent discusses melting temperatures, the ‘598 patent does not teach releasing DNA via melting.
D. New claim 21 (upon which claims 19-20 depend) recites release of a nucleic acid analyte from a tissue section in contact with one or more capture areas.” The ‘598 patent does not teach “release” from tissue.
Thus, because the cited limitations are missing from at least the ‘598 patent, the limitations constitute new matter.
Claim Rejections - 35 USC § 103
11. 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.
12. Claims 2-5, 7-8, 10, 12, 15-16, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Kincaid (U.S. Patent Application Publication No. US 2003/0186310 A1, published 2 October 2003) and Ahmadian et al. (U.S. Patent Application Publication No. US 2006/0088872 A1, published 27 April 2006).
Regarding claim 2, Kincaid teaches method comprising providing a substrate having a plurality of capture areas (i.e., features of a microarray; Abstract), each comprising a first oligomer test probe (Abstract), which is complementary to a nucleic acid analyte (i.e., a polynucleotide analyte; paragraphs 0052-0053) and a second oligonucleotide that identifies a location of the substrate, in the form of control probe that generates a control signal that is unique to the feature on the microarray (Abstract). The control probe is linked to the oligomer test probe (paragraph 0055), and the analyte (i.e., test target) hybridizes to the first oligonucleotide (i.e., oligomer test probe; paragraphs 0055 ad 0084 and Figure 4).
Kincaid also teaches the second (i.e., control) probe is labeled (Abstract), that the label is a primer for amplification or ligation (paragraph 0064). Kincaid further teaches:
At least one feature has a different control probe sequence (paragraph 0081);
The labels for the various control signals are different from one another and different from the labels associates with the test probe and target signals (paragraph 0076);
The signal emitted from the control label is unique to the control probe and is distinguishable from any other signals emitted from the microarray (paragraph 0075);
Labeled control targets hybridize to the control probes, resulting in at least two signals for each feature (paragraph 0020)
Thus, at least one capture area (i.e., the claimed “a capture area) comprise a second (control) oligonucleotide that corresponds to a location of the capture area on the substrate. Because the sequence of the second oligonucleotide is different (paragraph 0081), the signal therefrom corresponds specifically to that capture area.
Kincaid also teaches the methods have the added advantage of allowing normalization of signal trends across the array of capture areas (Abstract). Thus, Kincaid teaches the known techniques discussed above.
While Kincaid teaches the second oligonucleotide (i.e., control probe 110) is linked to the first oligonucleotide (i.e., oligomer test probe 120; Abstract, paragraph 0091, and Figure 4) and that the second oligonucleotide (i.e., control probe) is primer (paragraph 0064), Kincaid does not teach generating the claimed nucleic acid, which would contain the complements of both oligonucleotides (i.e., probes).
However, Ahmadian et al. teach methods wherein barcode sequences are used to hybridize to locations on an array (paragraph 0083). Ahmadian et al. also teach extension of the target using a probe (i.e., primer) having the barcode sequence attached thereto (paragraph 0083), wherein the barcode sequence is analogous to the second oligonucleotide (i.e., the control probe of Kincaid) and the target binding primer is analogous to the first oligonucleotide (i.e., the oligomer test probe of Kincaid). Ahmadian et al. also teach the methods allow for multiplex extension of variant target bases (paragraph 0083). Thus, Ahmadian 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 cited prior art to arrive at the instantly claimed method 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 method having the added advantage of allowing normalization of signal trends across the array of capture areas as explicitly taught by Kincaid (Abstract) and allowing for multiplex extension of variant target bases as explicitly taught by Ahmadian et al. (paragraph 0083). 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 methods useful for nucleic acid detection.
Regarding claims 3-4, the method of claim 2 is discussed above. Kincaid teaches the nucleic acid analyte is an RNA transcript (paragraph 0054).
Regarding claim 5, the method of claim 2 is discussed above. Kincaid teaches the analyte hybridizes to the first oligonucleotide (Abstract), and Ahmadian et al. teach targets hybridized to probes (paragraph 0083).
Regarding claims 7-8 and 18, the method of claim 2 is discussed above. Ahmadian et al. teach sequencing the template (i.e., claim 7; paragraph 0033), which is a portion of the generated nucleic acid of step (c) (i.e., claim 18), as well as PCR (i.e., the amplification of claim 8; paragraph 0193). Kincaid also teaches PCR (paragraph 0049).
It is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Thus, the claimed amplification and/or sequencing after generating the nucleic acid is an obvious variant of the steps of the cited prior art.
In addition, 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, counsel’s mere arguments cannot take the place of evidence in the record.
It is noted that the Response above should not be construed as an invitation to file an after final declaration. See MPEP 715.09.
Regarding claim 10, the method of claim 2 is discussed above. Ahmadian et al. teach the substrate is a slide (paragraph 0078).
Regarding claim 12, the method of claim 2 is discussed above. Kincaid also teaches fiducial makers on the substrate (paragraph 0006).
Regarding claim 15, the method of claim 2 is discussed above. Ahmadian et al. teach the target is cDNA (paragraph 0111), and Kincaid teaches cDNA (paragraph 0043). Thus, amplification of the linked first and second oligonucleotides results in second strand cDNA.
Regarding claim 16, the method of claim 15 is discussed above. Kincaid teaches release of DNA via melting, in the form of denaturation via heating (paragraph 0046). Ahmadian et al. teach melting (paragraph 0154).
With respect to the order of steps, it is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed denaturation after generating the nucleic acid is an obvious variant of the steps of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record, and that the Response above should not be construed as an invitation to file an after final declaration.
13. Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Kincaid (U.S. Patent Application Publication No. US 2003/0186310 A1, published 2 October 2003) and Ahmadian et al. (U.S. Patent Application Publication No. US 2006/0088872 A1, published 27 April 2006) as applied to claim 7 above, and further in combination with Schuster (Nature Methods, vol. 5, pages 16-18, published January 2008).
Regarding claim 9, the method of claim 7 is discussed above in Section 12.
Neither Kincaid nor Ahmadian et al. teach the sequencing is the functionally equivalent next generation sequencing.
However, Schuster teaches next generation sequencing has the added advantage of allowing sequencing at unprecedented speed (Abstract). Thus, Schuster teaches the known techniques discussed above.
It would therefore have alternatively been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have used the functionally equivalent next generation sequencing of Schuster to arrive at the instantly claimed method 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 method having the added advantage of allowing sequencing at unprecedented speed as explicitly taught by Schuster (Abstract). In addition, it would have alternatively been obvious to the ordinary artisan that the known techniques of Schuster could have been combined with the cited prior art with predictable results because the known techniques of Schuster predictably result in a functionally equivalent sequencing procedure.
14. Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Kincaid (U.S. Patent Application Publication No. US 2003/0186310 A1, published 2 October 2003) and Ahmadian et al. (U.S. Patent Application Publication No. US 2006/0088872 A1, published 27 April 2006) as applied to claim 2 above, and further in combination with Gumbrecht et al. (U.S. Patent Application US 2004/0029203 A1, published 12 February 2004).
Regarding claim 11, the method of claim 2 is discussed above in Section 12.
Neither Kincaid nor Ahmadian et al. teach flow cells.
However, Gumbrecht et al. teach methods utilizing arrays of DNA probes (paragraph 0005), wherein the arrays are withing a flow cell, which has the added advantage of allowing supply volumes for detection to be jointly accessible (paragraph 0013). Thus, Gumbrecht et al. teach the known techniques discussed above.
It would therefore have alternatively been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the cited prior art with the teachings of Gumbrecht et al. to arrive at the instantly claimed method 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 method having the added advantage of allowing supply volumes for detection to be jointly accessible to the array as explicitly taught by Gumbrecht et al. (paragraph 0013). In addition, it would have alternatively been obvious to the ordinary artisan that the known techniques of Gumbrecht et al. could have been combined with the cited prior art with predictable results because the known techniques of Gumbrecht et al. predictably result in arrays useful for nucleic acid detection.
15. Claims 13 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Kincaid (U.S. Patent Application Publication No. US 2003/0186310 A1, published 2 October 2003) and Ahmadian et al. (U.S. Patent Application Publication No. US 2006/0088872 A1, published 27 April 2006) as applied to claims 2 and 18 above, and further in combination with Erlander et al (U.S. Patent Application Publication No. US 2005/0239079 A1, published 27 October 2005).
Regarding claims 13 and 21, the methods of claims 2 and 18 are discussed above in Section 12.
Neither Kincaid nor Ahmadian et al. teach tissues.
However, Erlander et al teach methods where tissue sections are screened using an oligonucleotide microarray (paragraphs 0163 and 0170);
It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
In the instant case, because the whole tissue sections are analyzed on an oligonucleotide microarray, the nucleic acids are released from the tissue section on the array.
Alternatively, it is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, any order of steps, including applying the tissue section to the array and then releasing the nucleic acids, is obvious over the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record, and that the Response above should not be construed as an invitation to file an after final declaration.
Erlander et al. also teach the methods have the added advantage of allowing comparison of expression profiling between those who respond to a treatment (i.e., TAM) and those who do not (paragraph 0170). Thus, Erlander 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 cited prior art with the teachings of Erlander et al. to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantage of allowing comparison of gene expression of responders and non-responders to a drug treatment as explicitly taught by Erlander et al. (paragraph 0170). In addition, it would have been obvious to the ordinary artisan that the known techniques of Erlander et al. could have been combined with the cited prior art with predictable results because the known techniques of Erlander et al. predictably result in useful samples for analyzing gene expression.
16. Claims 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Kincaid (U.S. Patent Application Publication No. US 2003/0186310 A1, published 2 October 2003), Ahmadian et al. (U.S. Patent Application Publication No. US 2006/0088872 A1, published 27 April 2006), and Erlander et al (U.S. Patent Application Publication No. US 2005/0239079 A1, published 27 October 2005) as applied to claim 21 above, alternatively further in combination with Nguyen et al. (U.S. Patent Application Publication No. US 2004/0166553 A1, published 26 August 2004).
Regarding claims 19-20, the method of claim 21 is discussed above in Section 15.
Kincaid teaches the second oligonucleotide ( i.e., the control probe) generates a control signal that is unique to the feature on the microarray (Abstract). Thus, extending the linked first and second oligonucleotides and sequencing them results in obtaining the control probe sequence, which is indicative of a location (i.e., on the array).
Kincaid also teaches mapping of the sequencing information to a location on the substrate; i.e., detection allows mapping of each feature (i.e., to the microarray substrate (paragraph 0024).
Ahmadian et al. teach nucleic acids primers having barcodes (e.g., paragraph 0083); thus, extension of the target nucleic acid with barcoded primers results in generated nucleic acids having barcode sequences therein.
Erlander et al. also each identifying targets (e.g., alleles or polymorphisms) by mapping them to chromosomal locations (i.e., claims 19 and 20; paragraphs 0050 and 0029).
Thus, it would have been obvious for the control signals to correlate to or map to the location of the target nucleic acid analyte to a chromosome, which is a location within the tissue.
Alternatively, Nguyen et al. teach methods comprising the use of barcodes, which have the advantage of mapping to specific locations within a cell (paragraph 0461). Thus, Nguyen et al. teach the known techniques discussed above.
It would therefore have alternatively been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the cited prior art with the teachings of Nguyen et al. to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantage of allowing mapping to specific locations within the cells of the tissue as explicitly taught by Nguyen et al. (paragraph 0461). In addition, it would have alternatively been obvious to the ordinary artisan that the known techniques of Nguyen et al. could have been combined with the cited prior art with predictable results because the known techniques of Nguyen et al. predictably result in probes useful for analyzing cells.
Response to Arguments
17. Applicant's arguments filed 27 March 2026 (hereafter the “Remarks”) have been fully considered but they are not persuasive for the reasons discussed below
A. Pages 6-7 of the Remarks discuss the amendments and include the Interview Summary.
B. Pages 8-12 of the Remarks discuss the previous new matter rejections.
I. With respect to the arguments regarding the rejection of claim 2, Applicant cited paragraphs 0092, 0103, and 0115 of the instant specification.
However, none of these paragraph appear in the ‘598 Patent. Therefore, because the subject matter is not present in an application to which the instant Application claims priority, the subject matter constitutes new matter.
II. With respect to the citations of provisional Application 61/321,124, it is noted that claimed subject matter is considered essential subject matter. In order to incorporate essential material in the specification by reference to an unpublished U.S. Application, foreign application or patent, or publication, Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
III. Regarding Applicant’s citation of paragraphs 0047-0049 of the instant specification, it is reiterated that the claim encompasses each feature having the first and second nucleic acids separate from one another in a capture area; thus amplification to include both sequences (i.e., “generating a nucleic acid (emphasis added by the examiner) comprising (i)…and (ii)…” as claimed would be amplification to form a bridged structure between the two separate probes. The ‘598 patent does not yield teachings of this embodiment.
Thus, because the full scope of the claim is not supported by the ‘598 patent, the claim includes new matter.
IV. Regarding claim 13, it is reiterated that the ‘598 patent only teaches tissue section that themselves form an array (e.g., column 8, lines 30-45), but not teach oligonucleotide arrays contacted with tissue sections.
Thus, because the full scope of the claim is not supported by the ‘598 patent, the claim includes new matter.
V. Regarding claim 16, it is reiterated that the ‘598 Patent does not discuss melting to release a nucleic acid.
VI. The remaining new matter rejections are withdrawn in view of the amendments and/or arguments.
C. Applicant argues on pages 13-15 of the Remarks that Kincaid does not teach the second (control) probe corresponds to a location on the substrate because all control probes are allegedly the same sequence.
However, as noted in the rejections above, Kincaid teaches:
The second (i.e., control) probe is labeled (Abstract), that the label is a primer for amplification or ligation (paragraph 0064);
At least one feature has a different control probe sequence (paragraph 0081);
The labels for the various control signals are different from one another and different from the labels associates with the test probe and target signals (paragraph 0076);
The signal emitted from the control label is unique to the control probe and is distinguishable from any other signals emitted from the microarray (paragraph 0075); and
Labeled control targets hybridize to the control probes, resulting in at least two signals for each feature (paragraph 0020)
Thus, at least one capture area (i.e., the claimed “a capture area) comprise a second (control) oligonucleotide that corresponds to a location of the capture area on the substrate. Because the sequence of the second oligonucleotide is different (paragraph 0081), the signal therefrom corresponds specifically to that capture area.
D. Applicant’s remaining arguments regarding the previous obviousness rejections rely on alleged deficiencies previously addressed, which are unpersuasive for the reasons discussed above. Therefore, the claims remained rejected based on the prior art citations presented in the rejections.
E. Applicant’s arguments regarding the previous double patenting ejections have been considered, and the rejections are withdraw in view of the Terminal Disclaimer discussed above.
Conclusion
18. No claim is allowed.
19. 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).
20. 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.
21. 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.
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 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.
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Robert T. Crow
Primary Examiner
Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
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