DETAILED ACTION
Status of the Claims
Claims 42-61 are currently pending and are examined herein.
The following Office Action is in response to Applicant’s communication dated 08/24/2026. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Drawings
Applicant’s submission of replacement drawings on 08/24/2026 is acknowledged and doing so has overcome the previous objections.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 08/24/2026 is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the examiner.
Terminal Disclaimer
The terminal disclaimer filed on 08/24/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. 11,713,480 and 12,319,955 has been reviewed and is accepted. The terminal disclaimer has been recorded.
New Claim Rejections - 35 USC § 112(b) – Indefiniteness
Necessitated by Amendments
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 43-61 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 pre-AIA the applicant regards as the invention.
Claims 43-61 each depend from canceled claims and therefore the metes and bounds of the claim are unascertainable. In the interest of compact prosecution, these dependent claims will be interpreted as depending directly or indirectly from independent claim 42.
As per MPEP 2173: It is of utmost importance that patents issue with definite claims that clearly and precisely inform persons skilled in the art of the boundaries of protected subject matter. Therefore, claims that do not meet this standard must be rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph as indefinite. Further, as per MPEP 2173.02: If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. As currently written, the metes and bounds of the rejected claims are unascertainable for the reasons set forth above, thus the above claim(s) and all dependent claims are rejected under 35 USC 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
New Claim Rejections - 35 USC § 103
Necessitated by Amendments
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Frisén ‘275 and Frisén ‘106
Claims 42-61 are rejected under 35 U.S.C. 103 as being unpatentable over Frisén ‘275 (U.S. PGPub 2019/0203275 A1, cited in IDS of 10/10/2024, of record) in view of Frisén ‘106 (U.S. PGPub 2019/0017106 A1).
Regarding claim 42(in part), Frisén ‘275 discloses a method of generating a spatial transcriptomics gene expression image having subcellular resolution (e.g., as per para 0020-0022, 0054, and 0106-0107), comprising:
providing a flat array surface comprising high density clusters of probes, wherein a location of each cluster on said flat array surface is known (e.g., high-density arrays of capture probes as per para 0054-0055, wherein the capture probes comprise spatial tags as per para 0077-0078);
contacting said flat array surface with a tissue section such that RNA from cells in said tissue section hybridizes to capture domains of probes within the clusters (e.g., as per para 0084-0085 and 0094-0095 and Fig. 1, 7, and/or 8),
wherein a plurality of probes comprising a capture domain, a spatial barcode sequence, and a target RNA sequence or a complement thereof are formed (e.g., as per para 0077-0078 and 0099);
sequencing said sequencing library to generate sequencing data (e.g., as per para 0118); and
generating a spatial transcriptomics gene expression image having subcellular resolution from said sequencing data (e.g., as per para 0019-0020 and 0098).
However, it is noted that Frisén ‘275 is silent about the limitation regarding generating second strand copies of said plurality of probes and eluting said second strand copies from said array and generating a sequencing library from eluted second strand copies, as set forth in claim 42 steps (c)-(d).
Frisén ‘106 similarly discloses methods of measuring spatial transcriptomics in tissue samples by capturing mRNA on arrays of capture probes (e.g., as per para 0158-0160), but explicitly discloses generating second strand copies of said plurality of probes and eluting said second strand copies from said array (e.g., as per para 0163-0167) then generating a sequencing library (e.g., as per para 0179).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to perform the second strand synthesis directly on the array as per Frisén ‘106 in the subcellular resolution spatial transcriptomics method of Frisén ‘275. One of ordinary skill in the art would have been motivated to do so since this would avoid the need to ligate adaptors to the 3’ end of the cDNA first strand (e.g., as disclosed by Frisén ‘106 in para 0174).
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since both references are drawn to similar methods of measuring spatial transcriptomics in tissue samples by capturing mRNA on arrays of capture probes, noting that Frisén ‘106 states in para 0174 that “second strand synthesis may use a method of template switching … technology that is well established in the art” and may be performed using commercially available kits that are readily available.
Regarding claim 43, Frisén ‘275 discloses the above method, wherein the spatial barcode sequence of probes in a given cluster is identical, and wherein said spatial barcode sequence for each cluster is unique (e.g., as per para 0030 and 0043 of Frisén ‘275).
Regarding claim 44, Frisén ‘275 discloses the above method, wherein said flat array surface comprises 0.5-2 million clusters per 1 mm2 of surface (e.g., as per para 0054-0055 of Frisén ‘275).
Regarding claim 45, Frisén ‘275 discloses the above method, wherein said flat array surface comprises about 1.5 million clusters per 1 mm2 of surface (e.g., as per para 0054-0055 of Frisén ‘275).
Regarding claims 46-48, Frisén ‘275 discloses the above method, wherein each cluster comprises at least 800 probes (e.g., products of bridge amplification as per para 0121 and 0129 of Frisén ‘275).
Regarding claim 49, Frisén ‘275 discloses the above method, wherein each cluster has a diameter of 500-1200 nm (e.g., as per para 0055 of Frisén ‘275).
Regarding claim 50, Frisén ‘275 discloses the above method, wherein each cluster has an average diameter of 0.6 μm (e.g., as per para 0055 of Frisén ‘275).
Regarding claim 51, Frisén ‘275 discloses the above method, wherein said flat array surf ace comprises a material selected from glass, silicon, poly-L-lysine coated materials, nitrocellulose, polystyrene, cyclic olefin copolymers (COCs), cyclic olefin polymers (COPs), polyacrylamide, polypropylene, polyethylene and polycarbonate (e.g., as per para 0042 and 0048 of Frisén ‘275).
Regarding claim 52, Frisén ‘275 discloses the above method, wherein said capture domain is identical for each of the plurality of probes (e.g., as per para 0094 of Frisén ‘275).
Regarding claim 53, Frisén ‘275 discloses the above method, wherein said capture domain comprises a poly-T oligonucleotide comprising at least 10 deoxythymidine residues (e.g., as per para 0094 of Frisén ‘275).
Regarding claim 54, Frisén ‘275 discloses the above method, wherein each of the plurality of probes further comprises a sequencing barcode (e.g., as per EXAMPLE I of Frisén ‘275).
Regarding claim 55, Frisén ‘275 discloses the above method, wherein each of the plurality of probes further comprises one or more filler sequences (e.g., as per EXAMPLE I of Frisén ‘275).
Regarding claim 56, Frisén ‘275 discloses the above method, wherein each of the plurality of probes further comprises a unique molecular identifier (UMI) barcode sequence (e.g., as per para 0056-0058 of Frisén ‘275).
Regarding claim 57, Frisén ‘106 discloses the above method, wherein each of the plurality of probes further comprises a cleavage domain comprising a binding site for a restriction endonuclease (e.g., as per para 0105 of Frisén ‘106).
Regarding claim 58, Frisén ‘275 discloses the above method, further comprising imaging the tissue section (e.g., as per para 0107 of Frisén ‘275).
Regarding claim 59, Frisén ‘275 discloses the above method, further comprising correlating the known location of each cluster on said flat array surface with a corresponding location within said tissue section (e.g., as per para 0103-0109 of Frisén ‘275).
Regarding claim 60, Frisén ‘275 discloses the above method, wherein the distance between centers of said clusters is 1 μm or less (e.g., as per para 0054 of Frisén ‘275).
Regarding claim 61, Frisén ‘275 discloses the above method, wherein said clusters are produced by bridge amplification (e.g., as per para 0121 and 0129 of Frisén ‘275).
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Response to Arguments
The 08/24/2026 remarks argue: not all elements are taught.
Applicant's arguments have been fully considered but are moot due to the new grounds of rejection necessitated by Applicant’s amendments. To the extent possible, Applicant’s arguments have been fully addressed in the body of the rejection above.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEREMY FLINDERS whose telephone number is (571)270-1022. The examiner can normally be reached M-F 10-6:00 EST.
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, Heather Calamita can be reached on (571)272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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