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 .
Response to Amendment
The amendment filed January 28th, 2026 is acknowledged. Regarding the Office Action mailed October 31st, 2025:
The submission of the Sequence Listing and the substitute specification as required for the Nucleotide and/or Amino Acid Sequence Disclosures is acknowledged and accepted.
The rejections of claims 17 and 18 with regard to the clarity of the units used for the distance and diameter measurements set forth under 35 U.S.C. 112(b) are withdrawn in view of the amendments.
Maintained or modified rejections are set forth below, as necessitated by the amendments. Responses to arguments, if necessary, follow their respective rejection sections.
Claim Summary
Claims 1-2, 17-18, and 33 have been amended. Claims 3, 5, 12-13, 16, 21, 23, 25-28, 32, 35, and 37 have been canceled. Claims 1-2, 4, 6-7, 11, 14-15, 17-20, 22, 24, 29-31, 33-34, and 36 are pending. Claims 24, 29-31, 33-34, and 36 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 1-2, 4, 6-7, 11, 14-15, 17-20, and 22 are under examination and discussed in this Office action.
Claim Rejections - 35 USC § 112(b) - Modified - Necessitated by Amendment
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 1-2, 4, 6-7, 11, 14-15, 17-20, and 22 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 1 recites the limitation “wherein the one or more barcode labels are transferrable by diffusion from the matrix into a tissue sample upon contacting the substrate with the tissue sample”. It is unclear from this recitation how the barcode labels are being transferred by diffusion from the matrix into a tissue sample. It is generally understood by one of ordinary skill in the art that labels on a substrate (e.g. matrix) are immobilized to that substrate (see, for example, paragraphs [0072]-[0074] of Frisen (US20190024153A1; cited on the IDS filed August, 23rd, 2022)). Turning to the instant specification, a version of immobilization of the labels appears to be used, where the labels are spotted onto an agarose membrane (Page 24; Figures 9A-C). However, there is no subsequent step where the labels are released, or aspect of the barcode labels described related to being releasable, which would allow for transfer of the labels into a tissue sample in contact with the substrate. Even if there was a release step, it would be improper for the Examiner to read limitations from the specification into the claims (See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993)). For the purpose of compact prosecution, and based on general understanding of spatial barcoding of tissue samples, the limitation “wherein the one or more barcode labels are transferrable by diffusion from the matrix into a tissue sample upon contacting the substrate with the tissue sample” is interpreted as wherein the one or more barcode labels can interact with a tissue sample upon contacting the substrate with the tissue sample. Claims 2, 4, 6-7, 11, 14-15, 17-20, and 22 are also rejected here for their dependence on claim 1 and not further clarifying the identified issue.
It is also noted that claim 2 suffers from a similar issue to claim 1, where instead it is one or more reference labels that can be transferred from the matrix into a tissue sample. For the purpose of compact prosecution, the limitation “wherein the one or more reference labels are transferrable by diffusion from the matrix into a tissue sample upon contacting the substrate with the tissue sample” is interpreted as wherein the one or more reference labels can interact with a tissue sample upon contacting the substrate with the tissue sample. Claims 7 and 15 are also rejected here for their dependence on claim 2 and not further clarifying the identified issue.
Response to Arguments
Applicant's arguments filed January 28th, 2026 have been fully considered but they are not persuasive.
The Applicant first gives a summary of the rejection from the Examiner’s previous Office Action (Pages 7 and 8 of the Remarks filed January 28th, 2026). The Applicant then argues that the Examiner’s reference of Frisen does not substantiate the general knowledge of labels on a substrate are immobilized and impermissibly reads limitations from that document outside of the present application into the claims (Page of the Remarks filed January 28th, 2026). The Applicant further argues that there being no “steps” of label release is irrelevant because the pending claims are directed to a substrate and not a method (Page 8 of the Remarks filed January 28th, 2026). The Applicant then restates the new amendment to clarify claims 1 and 2, wherein it is now claimed that the one or more barcode labels are transferrable by diffusion from the matrix into a tissue sample upon contacting the substrate with the tissue sample, supported by paragraphs [0044] and [0046] of the published specification (Page 8 of the Remarks filed January 28th, 2026).
In response to these arguments, it is first noted that the reference of Frisen has been included to exemplify the idea that labels on a substrate are generally immobilized to that substrate and does not serve to read limitations into the claims from an outside source as argued. Given this general knowledge of labels being immobilized on a substrate, while the barcode labels are now claimed to be transferrable by diffusion, it is still unclear what aspect of the barcode labels allows them to be released from the matrix and transferred by diffusion into a tissue sample. In regards to the argument about “steps” being irrelevant, it is noted that the reference to “steps” merely serves as an aspect to describe the lack of clarity. Furthermore, this argument disregards that “there is no subsequent…aspect of the barcode labels described related to being releasable”, as was included in the prior rejection and is again included in the above rejection, which does address the structure of the substrate and not a method. Overall, as currently claimed, there is still no clear aspect of the barcode labels related to being releasable and thus capable of being transferrable by diffusion. Given these considerations, the arguments are not considered persuasive. Because of the continued lack of clarity, the previously applied interpretation of the limitation “wherein the one or more barcode labels are transferrable by diffusion from the matrix into a tissue sample upon contacting the substrate with the tissue sample” as wherein the one or more barcode labels can interact with a tissue sample upon contacting the substrate with the tissue sample has again been applied for examination purposes.
Claim Rejections - 35 USC § 103 - Modified - Necessitated by Amendment
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-2, 4, 6-7, 11, 14-15, 19-20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Frisen (US20190024153A1; cited on the IDS filed August, 23rd, 2022).
Regarding instant claim 1, Frisen teaches a substrate for spatially barcoding a tissue sample, comprising a matrix (Page 10, paragraph [0119]), wherein the matrix comprises: (a) a plurality of discrete labeling regions arranged in a pattern (Page 10, paragraph [0119]), and wherein each labeling region comprises one or more barcode labels (Page 8, paragraphs [0099]-[0100]; Page 10, paragraph [0119]), wherein the one or more barcode labels are transferrable by diffusion from the matrix into a tissue sample upon contacting the substrate with the tissue sample (Page 12, paragraph [0134]); and (b) a support (Pages 5-6, paragraph [0072]; Page 6, paragraph [0077]).
Frisen does not explicitly teach that the labeling regions are separated by non-labeling regions. However, the figures provide exemplary probe density arrangements that clearly show that there can be non-labeling regions between the labeling regions (Figures 10 and 11). Therefore, it would be obvious to one of ordinary skill in the art that the labeling regions of Frisen can be separated by non-labeling regions.
Regarding instant claim 2, Frisen teaches the substrate of Claim 1, wherein the matrix further comprises a plurality of discrete reference regions, wherein each reference region comprises one or more reference labels, wherein the one or more reference labels are transferrable by diffusion from the matrix into a tissue sample upon contacting the substrate with the tissue sample (Page 13, paragraphs [0143]-[0144]).
Regarding instant claim 4, Frisen teaches the substrate of Claim 1, wherein the matrix comprises a natural or synthetic polymer (Page 6, paragraph [0077]).
Regarding instant claim 6, Frisen teaches the substrate of Claim 1, wherein the one or more barcode labels are non-fluorescent (Page 8, paragraphs [0099]-[0100]; Page 10, paragraph [0119]).
Regarding instant claim 7, Frisen teaches the substrate of Claim 2, wherein the one or more reference labels comprise one or more fluorescent dyes and/or a staining dye (Page 13, paragraph [0144]).
Regarding instant claim 11, Frisen teaches the substrate of Claim 1, wherein the one or more barcode labels comprise a molecular tag indicating spatial coordinates within the matrix (Page 13, paragraph [0143]; Page 14, paragraph [0152]).
Regarding instant claim 14, Frisen teaches the substrate of Claim 1, wherein each labeling region comprises a unique combination of the one or more barcode labels (Page 8, paragraph [0098]-[0100]).
Regarding instant claim 15, Frisen teaches the substrate of Claim 2, wherein the labeling regions and/or reference regions are prepared by spotting droplets of a solution comprising the one or more barcode labels onto the matrix (Page 26, paragraph [0362]).
Regarding instant claim 19, Frisen teaches the substrate of Claim 1, wherein the labeling regions are arranged in a grid (Figure 1).
Regarding instant claim 20, Frisen teaches the substrate of Claim 1, wherein the substrate comprises about 3,000 unique labeling regions in a 10 mm by 10 mm area (Page 11, paragraph [0122]: where 1 cm2 is equivalent to 10mm by 10mm).
Regarding instant claim 22, Frisen teaches the substrate of Claim 1, wherein the support comprises glass or synthetic polymer (Page 6, paragraph [0077]).
Claims 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Frisen (US20190024153A1; cited on the IDS filed August, 23rd, 2022), as applied to claims 1-2, 4, 6-7, 11, 14-15, 19-20, and 22, in view of Stahl (Visualization and analysis of gene expression in tissue sections by spatial transcriptomics, Science, July 2016, 353, 78-82; cited on the IDS filed August 23rd, 2022).
Regarding instant claim 17, Frisen teaches the substrate of Claim 1.
Frisen does not teach wherein the labeling regions have a distance of about 200 um between the centers of the labeling regions.
Stahl, in the same field of endeavor, teaches wherein the labeling regions have a distance of about 200 um between the centers of the labeling regions (Page 78, column 3, paragraph 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the substrate of Frisen with the center distances of Stahl. Since both Frisen and Stahl are in the same field of endeavor, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to applying a known technique to a known device to yield predictable results (see MPEP 2141(III)). It is known that a substrate for spatial barcoding of a tissue sample can have labeling regions with center distances of 200 um, therefore it would be obvious that a similar substrate can have the same center distances.
Regarding instant claim 18, Frisen teaches the substrate of Claim 1.
Frisen does not teach wherein the labeling regions have a diameter of from 1 um to 200 um, or from 50 um to 200 um.
Stahl, in the same field of endeavor, teaches wherein the labeling regions have a diameter of 100 um (Page 78, column 3, paragraph 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the substrate of Frisen with the region diameters of Stahl. Since both Frisen and Stahl are in the same field of endeavor, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to applying a known technique to a known device to yield predictable results (see MPEP 2141(III)). It is known that a substrate for spatial barcoding of a tissue sample can have labeling regions with diameters of 100 um, therefore it would be obvious that a similar substrate can have the same labeling region diameters.
Response to Arguments
Applicant's arguments filed January 28th, 2026 have been fully considered but they are not persuasive.
The Applicant first gives a short summary of the Examiner’s previous rejections (Page 9 of the Remarks filed January 28th, 2026). The Applicant includes citations from the MPEP regarding the prior art including every element claimed for a prior obviousness rejection (Page 9 of the Remarks filed January 28th, 2026). The Applicant argues that the amendment to claims 1 and 2, wherein the barcode labels are transferrable by diffusion, is not taught by the Frisen reference (Pages 9 and 10 of the Remarks filed January 28th, 2026). The Applicant includes several citations of the teachings of Frisen regarding release of tagged DNA molecules, noting that there is no transfer of barcodes by diffusion (Page 10 of the Remarks filed January 28th, 2026). The Applicant also cites that Frisen emphasizes tagged nucleic acids do not transfer to tissue at all (Page 10 of the Remarks filed January 28th, 2026). The Applicant argues, given these considerations of Frisen, that it generally teaches on capture of target molecules on capture probes immobilized on an array and not tags moving into tissues (Page 11 of the Remarks filed January 28th,m 2026). The Applicant also notes that Stahl fails to cure the noted deficiencies of Frisen (Page 11 of the Remarks filed January 28th, 2026).
In response to these arguments, it is noted that, given the lack of clarity of the claim limitation “wherein the one or more barcode labels are transferrable by diffusion from the matrix into a tissue sample upon contacting the substrate with the tissue sample”, the Examiner has applied the broadest reasonable interpretation of this limitation for examination purposes. As stated above, this interpretation is wherein the one or more barcode labels can interact with a tissue sample upon contacting the substrate with the tissue sample. Given this interpretation, it is currently found that Frisen adequately teaches all aspects of the invention as currently claimed. Therefore, the arguments are not found persuasive.
Conclusion
All claims stand rejected.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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