DETAILED 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 .
Claim Rejections - 35 USC § 112
2. 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.
3. Claims 13-16 and 35-47 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. Claim 13 has been amended to recite the phrase “wherein the click-enabled moiety reacts with a cell functionalizing probe.” This phrase describes a process limitation, which does not provide additional limitations to the claimed structure of the product. It is unclear if this limitation is intended to convey that the “click-enabled moiety” is capable of reacting with a cell functionalizing probe or if the “click-enabled moiety” has already been reacted with a cell functionalizing probe. The metes and bounds of this phrase’s effect on the product structure are unclear and therefore the claim is indefinite.
B. Claim 38 provides the structure of the fluorophore comprised by the barcoded tag of claim 15. The structure contains R groups 3-9, but none of the claimed R groups provide an attachment site to the barcoded tag. It is unclear how this fluorophore is supposed to be used with the barcoded tag of claim 15 and therefore the claim is indefinite.
C. Claim 41 states that the photocaged fluorophore of claim 40 is the given structure, however this structure provides no indication of the site at which it attaches to the barcoded tag of claim 15 from which claim 40 depends. The attachment chemistry of the provided structure is unclear and therefore the claim is indefinite.
D. Claim 42 states that the spatial barcode is “compatible with single cell RNA sequencing,” however, neither the claim language nor applicant’s specification provides clarity regarding how exactly the spatial barcode “is compatible.” Does the spatial barcode not interfere with scRNA-seq? Does the spatial barcode directly label mRNA from a cell? Does the spatial barcode become labeled by a polyT capture sequence commonly employed in scRNA-seq? The limitations this claim places on the barcoded tag structure are unclear and therefore the claim is indefinite.
E. Claim 44 states that the spatial barcode is “a smart-seq2-enabled barcode,” however, neither the claim language nor applicant’s specification provides clarity regarding how exactly the spatial barcode “is smart-seq2-enabled.” Does the spatial barcode not interfere with smart-seq2-based scRNA-seq? Does the spatial barcode directly label mRNA from a cell? Does the spatial barcode become labeled by a polyT capture sequence commonly employed in smart-seq2 library prep? The limitations this claim places on the barcoded tag structure are unclear and therefore the claim is indefinite.
F. Claim 45 states that the spatial barcode is “a Poly dT capture bead-enabled barcode,” however, neither the claim language nor applicant’s specification provides clarity regarding how exactly the spatial barcode “is Poly dT capture bead-enabled.” Is this spatial barcode captured by Poly dT beads? Does the spatial barcode directly label mRNA from a cell? Is it specifically not captured by Poly dT beads (i.e., it is enabled in that it does not interfere with the expected function of Poly dT beads in a desired workflow)? The limitations this claim places on the barcoded tag structure are unclear and therefore the claim is indefinite.
G. All remaining claims not discussed here are rejected for being dependent on a previously rejected claim.
Claim Rejections - 35 USC § 102
4. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
5. Claims 13-16, 35-36 and 46-47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Seckute et al (Rapid oligonucleotide-templated fluorogenic tetrazine ligations, Nucleic Acids Research, 41, 15, published 1 August 2013).
Regarding claim 13, the preamble recites “a cell functionalizing barcoded tag” and this is interpreted, in accordance with the MPEP, as an intended use of the barcoded tag and as such does not provide additional structural limitations for the claimed invention. Seckute teaches a polyadorned molecule (FIG 1b, the drawn ribose sugar moiety) comprising 3 substituents (FIG 1b; the “T” nucleobase, the 5' phosphate group, and the 3' phosphate group). Seckute teaches that the substituents comprise a click-enabled moiety (FIG 1b, the tetrazine present on the 5' phosphate) and an oligonucleotide (FIG 1b, the remaining nucleotide sequence on the 3' phosphate group). It is noted that any oligonucleotide sequence is sufficient to meet the generic limitation of “a spatial barcode.”
It is noted that claim 13 has been amended to recite “wherein the click-enabled moiety reacts with a cell functionalizing probe.” The method step ‘reacts with’ is not a structural limitation, and therefore does not further limit the claimed structure in claim 13.
Regarding claims 14 and 15, Seckute teaches that the barcoded tag comprises a label and that the label is a fluorophore (FIG 1b and FIG 2, the fluorescein tag on the “T” nucleobase).
Regarding claim 16, it is noted that the limitations of this claim only limit the embodiment of the invention wherein the label is a peptide, but claim 15 does not require that the label is a peptide. Therefore claim 16 does not provide additional limitations regarding the embodiment wherein the label is a fluorophore.
Regarding claim 35 and 36, these claims provide limitations for the cell functionalizing probe that the cell functionalizing barcode tag of claim 13 reacts with, therefore these limitations do not further limit the structure of claim 13. The cell functionalizing probe is not part of the claimed structure disclosed in claim 13 (i.e., the cell functionalizing barcode tag), and insofar as the final clause of claim 13 is considered functional language it is noted that the tetrazine moiety of the barcoded tag of the prior art comprises a click-enabled tetrazine moiety that is functionally capable of reacting with a strained alkene (i.e., a bio-orthogonal reactive group).
Regarding claim 46, the spatial barcode taught by Seckute comprises a 5' tetrazine moiety (i.e., a 5' handle; FIG 1b).
Regarding claim 47, without further limitations to the claim the spatial barcode taught by Seckute is considered an elongated spatial barcode compared to any shorter spatial barcode.
6. Claims 13-16, 35-41 and 46-47 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Crawford et al (United States Patent Application No. US20170204457, effectively filed 31 March 2015).
Regarding claims 13-15, the preamble recites “a cell functionalizing barcoded tag” and this is interpreted, in accordance with the MPEP, as an intended use of the barcoded tag and as such does not provide additional structural limitations for the claimed invention. Crawford teaches a ssDNA structure comprising an azide group at its 5' terminus and a biotin at its 3' terminus (i.e., a polyadorned molecule with 2-5 substituents; [0160]). The azide is a click-enabled moiety, without any additional limitations to the claim the ssDNA region is sufficient to meet the generic limitation of “a spatial barcode,” and the 3' terminal biotin is a label.
Regarding claim 16, it is noted that the limitations of this claim only limit the embodiment of the invention wherein the label is a peptide, but claim 15 does not require that the label is a peptide. Therefore claim 16 does not provide additional limitations regarding the embodiment wherein the label is biotin.
Regarding claim 35 and 36, these claims provide limitations for the cell functionalizing probe that the cell functionalizing barcode tag of claim 13 reacts with, therefore these limitations do not further limit the structure of claim 13. The cell functionalizing probe is not part of the claimed structure disclosed in claim 13 (i.e., the cell functionalizing barcode tag), and insofar as the final clause of claim 13 is considered functional language it is noted that the tetrazine moiety of the barcoded tag of the prior art comprises a click-enabled azide moiety that is functionally capable of reacting with an alkyne (i.e., a bio-orthogonal reactive group).
Regarding claims 37, Crawford teaches a 3' biotin label ([0160]).
Regarding claims 38-41, it is noted that the limitations of these claims only limit the embodiment of the invention wherein the label is a fluorophore, but claim 15 does not require that the label is a fluorophore. Therefore claims 38-41 do not provide additional limitations regarding the embodiment wherein the label is biotin and are each anticipated by Crawford.
Regarding claim 46, the spatial barcode taught by Crawford comprises a 5' azide moiety (i.e., a 5' handle; [0160]).
Regarding claim 47, without further limitations to the claim the spatial barcode taught by Crawford is considered an elongated spatial barcode compared to any shorter spatial barcode.
Claim Rejections - 35 USC § 103
7. 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.
8. 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.
9. Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Seckute et al (Rapid oligonucleotide-templated fluorogenic tetrazine ligations, Nucleic Acids Research, 41, 15, published 1 August 2013) in view of Wysocki et al (Facile and general synthesis of photoactivatable Xanthene dyes, Angewandte Chemie International Edition, 50, 47, 11206-11209, published 14 November 2011).
Regarding claim 40, the method of claim 15 is discussed fully above and incorporated here. Seckute does not teach that the fluorophore is a photocaged fluorophore.
However, Wysocki teaches the preparation of photoactivatable dyes (i.e., photocaged fluorophores; Schemes 1-3).
It would have been obvious to one having ordinary skill in the art to have modified the fluorophore taught by Seckute with the photocaging moieties taught by Wysocki to arrive at the instantly claimed invention with a reasonable expectation of success. The ordinary artisan would have been motivated to make this modification in order to produce fluorescent tags having high contrast and reduced backgrounds. In addition, one having ordinary skill in the art would have recognized that the known techniques in the cited references could have been combined with predictable results because the known techniques in the cited references predictably result in the photocaging of fluorophores having similar chemical structures.
Response to Arguments
10. Applicant's arguments filed 29 August 2025 have been fully considered but they are not persuasive.
Applicant argues that the amendments to claim 13 overcome Seckute’s anticipation rejection, however, applicant’s amendments merely add functional limitations describing the intended use of the claimed product. These functional limitations do not introduce additional structural limitations into the claimed product and therefore applicant’s argument is not persuasive and the rejection is maintained.
Applicant has overcome the previous Double Patenting rejections because copending application 18/952,340 has gone abandoned.
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.
Conclusion
11. No claims are allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN ELLIS YOUNG whose telephone number is (703)756-5397. The examiner can normally be reached M-F 0730 - 1700.
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/BRIAN ELLIS YOUNG/Examiner, Art Unit 1684 /JULIET C SWITZER/Primary Examiner, Art Unit 1682