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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/28/2026 has been entered.
Status of the Claims
Claims 22, 38, and 42 have been amended. Claims 22-36 and 38-42 are pending after election and examined herein.
Priority
This application, filed on 02/22/2022, claims priority to provisional application 63/152,2021 filed on 02/23/2021. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 02/23/2021.
Amended Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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 22-36 and 38-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2020/123305A2 “Generating Capture Probes for Spatial Analysis” (published 06/18/2020, herein referred to as Schnall).
Regarding claim 22, 38, and 42, Schnall discloses an array for detecting analytes (Abstract, p. 3, line 15) on a patterned substrate (p. 123, lines 6-8) with a plurality of oligonucleotide structures (p. 3, lines 15-16) in a plurality of binding sites (p. 123, lines 33-34. The oligonucleotide structures make up supramolecular structures including a core structure (“first oligonucleotide”, p. 12, lines 15-16) that is coupled to the substrate (p. 13, lines 25-27), a capture barcode (“second oligonucleotide”, p. 12, lines 17-18) containing a “spatial barcode” that is attached to “an unattached end of the first oligonucleotide”, and a capture molecule (“third oligonucleotide”, p. 13, lines 19-21) containing a “capture domain” (p. 15, lines 13-14) attached to “an unattached end of the second oligonucleotide” (p. 13, lines 19-21). Schnall discloses that the substrate is patterned (p. 143, lines 9-14). Schnall discloses the use of an oligonucleotide (Figure 24, “A”, p. 465, lines 2-7) attached to the substrate, i.e. an anchor oligonucleotide, to produce the first oligonucleotide with a primer. The use of this oligonucleotide results in a core structure comprising a plurality of core molecules including the anchor oligonucleotide and the first oligonucleotide. Schnall discloses that the analyte is a protein or peptide (p. 8, lines 3-5).
Schnall does not specifically disclose an embodiment wherein the capture barcode comprises a first capture linker, a second capture linker, and a capture bridge disposed between the first and second capture linkers, wherein the first capture linker is bound to a first core linker that is bound to a first location on the core structure, and wherein the capture molecule and the second capture linker are linked together through binding to a third capture linker.
Schnall does disclose that the first, second, and third oligonucleotides are attached to each other end-to-end (p. 390, lines 19-27). Schnall discloses oligonucleotides can be hybridized together with splint sequences in order to ligate oligonucleotides together to construct complete constructs (p. 341, line 30 – p. 342, line 2. For example, see Figure 44). Schnall discloses that the use of splint oligos to facilitate ligation between oligonucleotides requires ligation handles, i.e. linkers, on the oligonucleotides that are ligated, i.e. bound, together. Following this mechanism of ligation between the first, second, and third oligonucleotides, the second oligonucleotide would comprise the barcode bridge with a first capture linker, i.e. ligation handle, to bind to the first core linker, i.e. ligation handle on the first oligonucleotide, and a second capture linker to bind to the third oligonucleotide, i.e. capture molecule with a third capture linker (See diagram below added for clarity).
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It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the splint oligo-based ligation method taught by Schnall to ligate the three disclosed oligonucleotides together to form the disclosed capture oligo. Doing so is considered to be using a known method to obtain known results, as disclosed by Schnall. An artisan would have a reasonable expectation of success as the method to ligate oligos together is routine in the art and Schnall discloses that this method can be used to form oligo constructs in the disclosed array.
Regarding claim 23, Schnall discloses that the core structure, “first oligonucleotide,” can be identical to each other (p. 391, lines 7-10) stating that “the first oligonucleotide can be understood as a common oligonucleotide ‘lawn’ across the surface of the substrate that does not differ in sequence.”
Regarding claim 24, Schnall discloses that the capture barcode, “second oligonucleotide,” can include a “unique molecular identifier” (p. 367, lines 29-31).
Regarding claim 25, Schnall discloses that the substrate can be a solid array (p. 32, line 4) or on a porous membrane (p. 32, line 11).
Regarding claim 26, Schnall discloses that the capture probe is made up of oligonucleotides, which are nanostructures (p. 3, lines 15-16).
Regarding claim 27, Schnall discloses that the core structure is an oligonucleotide (“first oligonucleotide”, p. 12, lines 15-16) which is a nanostructure.
Regarding claim 28, Schnall discloses that the array “has a plurality of capture probes…spotted, printed, or synthesized on the array with a pre-determined pattern” (p. 143, lines 9-14). These capture probes each comprise a core structure, as described regarding claims 22, 38 and 42 above (“first oligonucleotide”, p. 12, lines 15-16).
Regarding claim 29, Schnall discloses that the core structure is coupled to the substrate (“first oligonucleotide”, p. 12, lines 15-16) via its 3’ or 5’ end.
Regarding claim 30, Schnall discloses a plurality of supramolecular structures, i.e. “capture probes”, bound to a plurality of analytes (p. 11, line 5).
Regarding claim 31, Schnall discloses a plurality of detector molecule assemblies, i.e. “capture probes”, bound to a plurality of analytes (p. 11, line 5).
Regarding claim 32, as described regarding claims 22, 38 and 42, Schnall discloses that each detector molecule assembly includes a detector molecule, i.e. the third oligonucleotide (p. 13, lines 19-21), linked to a detector barcode, i.e. the spatial barcode, via the second oligonucleotide (p. 12, lines 17-18).
Regarding claim 33, as described regarding claims 22, 38 and 42, Schnall discloses that each detector molecule assembly, i.e. capture probe, comprises a core structure (“first oligonucleotide”, p. 12, lines 15-16) that is coupled to the substrate (p. 13, lines 25-27), a capture barcode (“second oligonucleotide”, p. 12, lines 17-18) containing a “spatial barcode” that is attached to “an unattached end of the first oligonucleotide”, and a capture molecule (“third oligonucleotide”, p. 13, lines 19-21) containing a “capture domain” (p. 15, lines 13-14) attached to “an unattached end of the second oligonucleotide” (p. 13, lines 19-21).
Regarding claim 34, Schnall discloses that the substrate can be a porous membrane (p. 32, line 10-11).
Regarding claim 35, Schnall discloses that the substrate can be a hydrogel (p. 32, lines 10-11).
Regarding claim 36, Schnall discloses that the substrate can be flat (p. 123, lines 4-5).
Regarding claim 37, Schnall discloses that the supramolecular structure contains only one capture molecule, i.e. “third oligonucleotide”, by virtue of attaching to the only one unattached end of the second oligonucleotide (p. 15, lines 10-14).
Regarding claim 39, Schnall discloses that “fiducial markers can be included on the substrate” (p. 124, lines 21-22) to “provide guidance for correlation spatial information with the characterization of the analyte of interest” (p. 124, lines 18-19).
Regarding claim 40, Schnall discloses that the substrate can be passivated with polyethylene glycol (p. 238, lines 17-18).
Regarding claim 41, Schnall discloses that “the surface of the substrate can be modified so that discrete sites [i.e. binding sites] are formed that can only have or accommodate a single feature [i.e. supramolecular structure]” (p. 123, lines 23-24. Exemplary text added).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 93 and 94 of copending Application No. US 2024/0118274 A1 (referred to as Gopinath) in view of Schnall.
Claim 93 of Gopinath recites a system for detecting analytes comprising a substrate with a plurality of supramolecular structures (lines 1-2), which is an array. Reference recites that the supramolecular structure comprises a capture molecule to bind to the analyte and a barcode.
Claim 94 of Gopinath recites that the barcode is linked to the capture molecules (lines 1-2).
Gopinath does not recite a core structure coupled to the substrate via an oligonucleotide anchor, how the components of the supramolecular structure are connected, or wherein the analyte is a protein, peptide, peptide fragment, or a combination thereof.
However, Schnall discloses an array of supramolecular structures including a core structure (“first oligonucleotide”, p. 12, lines 15-16) that is coupled to the substrate (p. 13, lines 25-27), a barcode (“second oligonucleotide”, p. 12, lines 17-18) attached to “an unattached end of the first oligonucleotide”, and a capture molecule (“third oligonucleotide”, p. 13, lines 19-21) attached to “an unattached end of the second oligonucleotide” (p. 13, lines 19-21). As taught in Schnall, the use of the core first nucleotide “effectively acts as the starting point on the spatial array for the spatially directed in situ synthesis of the…barcode” (p. 391, lines 10-12). ). Schnall discloses the use of an oligonucleotide (Figure 24, “A”, p. 465, lines 2-7) attached to the substrate, i.e. an anchor oligonucleotide, to produce the first oligonucleotide with a primer. The use of this oligonucleotide results in a core structure comprising the anchor oligonucleotide and the first oligonucleotide. Schnall discloses that the analyte is a protein or peptide (p. 8, lines 3-5).
Thus, it would have been obvious to one of ordinary skill in the art at the time the application was filed to modify the system taught in Gopinath by including a core structure and linking the core structure, barcode, and capture molecule together, as taught by Schnell because doing so would enable the spatially-directed synthesis of the barcode and, as a result, be able to identify the location of bound analytes on the array with the use of the synthesized spatial barcode. A skilled artisan would have had a reasonable expectation of success in constructing the supramolecular structures with a core structure because the use of core structures in analyte arrays is well known in the art and linking oligonucleotides together is a routine process.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 01/28/2026 have been fully considered but they are not persuasive for the following reasons:
Regarding the remarks on page 10 over the rejection of claims 22-36 and 38-42 under 35 U.S.C. 103, Applicant argues that Schnall does not teach a core structure containing a plurality of nucleic acid strands.
This argument is not persuasive. As discussed in the amended rejection above, Schnall teaches a core structure comprising the “first oligonucleotide” and another oligonucleotide coupled to the surface which is used to generate the first oligonucleotide.
Further regarding the remarks on page 10, Applicant argues that Schnall does not teach a capture barcode coupled to the core structure.
This argument is not persuasive. As discussed in the rejection above, Schnall teaches a capture barcode (“second oligonucleotide”, p. 12, lines 17-18) containing a “spatial barcode” that is attached to “an unattached end of the first oligonucleotide”.
Further regarding the remarks on page 10, Applicant argues that Schnall does not teach an anchor molecule linking the core structure to the substrate.
This argument is not persuasive. As discussed in the amended rejection above, Schnall teaches a core structure comprising the “first oligonucleotide” and another oligonucleotide, which is considered an anchor, coupled to the surface which is used to generate the first oligonucleotide.
Regarding the rejection of claim 22 by Nonstatuatory Double Patenting, the rejection is maintained and will not be held in abeyance.
Conclusion
No claims are allowable.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 March 9, 2026