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 .
Claim Status
Claims 1-5, 7-14, 23, and 32-36 are pending and under examination. Claims 6, 15-22, 24-31, and 37-45 were previously cancelled. Claims 1 and 35 are the only independent claims, and have both been amended.
Response to Arguments
Rejections Maintained
The rejection of claims 1-6, 7-14, 23, and 32-36 under 35 U.S.C. 103 as being unpatentable over Peterson et al. (US 2018/0208975 A1) in view of Stoeckius et al. (US 2018/0251825 A1) and further in view of Gunderson (US 2018/0273933 A1) is maintained.
Applicant's arguments filed 04/16/2026 have been fully considered but they are not persuasive. The applicant erroneously recalls the teachings of Peterson and their own previous remarks describing Peterson Fig. 2 stating that “As discussed in the previous Amendment and Reply filed October 7, 2025, Peterson discloses a method in which Oligo A and Oligo B are first attached to the target molecule and then when Oligo A and Oligo B are in proximity to each, a third molecule - a protein detection probe – hybridizes to Oligo A or both oligos.” However, this is not what is not what is taught by Peterson, a fact that was acknowledged in the previous Amendment and Reply to Office Action dated October 7, 2025.
As an initial matter, Applicant’s argument presupposes that the limitation requiring two proximity probes whose respective oligonucleotide domains interact with one another (the IMR limitation) is absent from the cited art and must instead be supplied by a reason or motivation to combine teachings across references. This is incorrect. Peterson discloses this limitation expressly and in a single reference. Peterson paragraph [0006] describes that “Oligo A comprises 5' to 3'universal primers (Read 1 or Read 2 Illumina sequences), Ab barcode A, Oligo A and Oligo B complementary sequence. Oligo B comprises 5' to 3' extension product and protein detection probe complementary sequence, Ab barcode B, Oligo A and Oligo B complementary sequence.” Teaching that both Oligo A and Oligo B comprise an Oligo A and Oligo B complementary sequence. After binding to a protein target, these oligos hybridize via the complementary sequence present in each oligo and are extended to include the components of the corresponding oligo, precisely the claimed IMR interaction.
Because this limitation is disclosed expressly within Peterson itself, no separate showing of a reason to combine teachings, nor a reasonable expectation of success in combining references is required to establish that the limitation is taught. The Applicant’s remarks do not even acknowledge the disclosure of Peterson [0006] and Fig. 2, which was specifically identified in the prior Office Action (pg. 3, ¶2) and previous Amendment and Reply to Office Action from the applicant Dated October 7, 2025, disclosing this limitation.
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Therefore, it was already of record that Peterson teaches an inter-molecular reacting region on each of the probes, wherein the IMR of the first oligonucleotide domain interacts with the IMR of the second oligonucleotide domain.
In response to applicant's argument that Peterson discloses a sequence of events different from claim 1 because, in Peterson, a third molecule, the protein detection probe hybridizes to Oligo A and/or Oligo B after Oligo A and Oligo B have attached to the target, whereas the first and second proximity probes of claim 1 allegedly attach to the analyte “without the need for a third molecule.” This argument is not persuasive.
First, the claim recites an open transitional phase (“comprising”), and as such does not exclude the presence or use of additional unrecited molecules, probes, or hybridization events, (see MPEP 211.03). The fact that Peterson’s assay additionally employs a third molecule at a later point in the assay does not remove Peterson’s teaching of the first and second proximity probes and their interacting oligonucleotide domains from the scope of claim 1, since claim 1 does not require , and does not exclude, the absence of a third molecule.
Second, claim 1 does not recited or require any particular sequence or order of steps beyond what is logically necessitated by the claim language itself, and no such order is argued by the Applicant to be required, (See MPEP 2111.04). Even accepting Applicant’s characterization of Peterson’s sequence of events, the claimed IMR interaction is satisfied by Peterson’s express disclosure that Oligo A and Oligo B each comprise an “Oligo A and oligo B complementary sequence” that hybridizes between the two probes upon their co-binding to the analyte, (see Peterson [0006]). This interaction occurs directly between the first and second proximity probes, independent of, and prior to, any subsequent involvement of the protein detection probe. Peterson’s later use of a third molecule to introduce a cell barcode and UMI into the resulting extension product does not negate, alter, or detract from Peterson’s express teaching of the claimed IMR interaction between the first and second proximity probes.
Applicant next argues that Stoeckius does not disclose two polymer constructs that interact with each other via an inter-molecular reacting region. This argument is not persuasive because it is not commensurate with the basis of the rejection. The rejection does not rely on Stoeckius to teach the claimed interaction between the IMR of the first proximity probe and the IMR of the second proximity probe, that limitation is taught by Peterson, as discussed above and in the rejection of record. Stoeckius is relied upon only for its teaching of incorporating a UMI directly within an antibody-conjugated oligonucleotide domain, adjacent to a barcode identifying the bound ligand. In response to the applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant’s argument that Stoeckius individually lacks a teaching for which it was not cited does not address, and therefore does not rebut, the actual basis of the rejection. Applicant summarily argues that Gunderson does not teach all of the limitations of Claim 1, without citing the specific teachings for which Gunderson is relied upon and does not rebut the actual basis of the rejection.
The applicants argues, see Amendment and Reply to Office Action pg. 8, that “the combination of Peterson, Stoeckius, and Gunderson fails to teach or provide a reason for one of ordinary skill in the art to use 2 proximity probes that interact with each via its respective IMRs as claimed and fails to provide a reasonable expectation of success.” This argument is not persuasive and appears to be on a mischaracterization of the Peterson reference and of the rejection of record as discussed above.
Conclusion
No claim is allowed.
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.
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/MATTHEW HAROLD RAYMONDA/ Examiner, Art Unit 1684 /AARON A PRIEST/Primary Examiner, Art Unit 1681
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