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 .
Applicants' arguments, filed January 27, 2026, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Drawings
The drawing was received on January 27, 2026. The drawing is acceptable.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 5 – 12 and 17 – 20 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nakamoto et al. (US 2020/0248263). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed November 4, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds that Nakamoto cannot achieve the significant function of the present invention as it does not possess a cellular dye configured to bind to the endogenous cellular component but rather relies on an antibody for target binding and a fluorescent dye incorporated within the barcode of the composition rather than configured to bind to a cellular component.
These arguments are unpersuasive. That additional elements are present in the constructs of Nakamoto et al. does not patentably distinguish the instant claims as the claimed composition comprises an oligonucleotide conjugated to a cellular dye. The particular nature of the conjugation between the oligonucleotide barcode and cellular dye is not further claimed. Hoechst 33342 and Hoechst 33258 are disclosed by Nakamoto et al. and instant claim 8 indicates that Hoechst cellular dyes are species within the genus of cellular dyes configured to bind to at least one endogenous cellular component. That the prior art does not use the same language and/or functional description of the fluorophore as the instant application and claims does not patentably distinguish the instant claims as conjugates of Hoechst with an oligonucleotide are disclosed by Nakamoto. Applicants have not established that the structure of the fluorophore such as Hoechst must be further modified in order to render the cellular dye “configured to bind to the endogenous cellular components”. The functions of a molecule cannot be separated from its structure. Claim interpretation including the intended use recitations was discussed on p 5 of the November 4, 2025 Office Action. The amendments to the claims do not alter the interpretation of the intended use of the claimed composition and the arguments do not establish the constructs of Nakamoto et al. are incapable of carrying out the intended use of binding to and quantifying endogenous cellular components.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 2, 5 – 12 and 17 – 20 are rejected under 35 U.S.C. 103 as being unpatentable over Nakamoto et al. (US 2020/0248263) in view of Zhu et al. (Acc Chem Res, 2016) and Cai et al. (US 10,266,876). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed November 4, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds that Nakamoto does not describe the feature of a cellular dye configured to bind to the endogenous cellular component and does not suggest modification of the disclosed invention to include the claimed feature. Nakamoto discloses oligonucleotide-conjugated antibodies for cell sorting and sequence based protein expression profiling. Calcein AM is employed solely as a conventional live-cell viability stain for flow cytometric gating and is not conjugated to an oligonucleotide barcode, not sequenced and not used as part of any barcoding, indexing or quantitative sequence starts. While Figure 9 shows a fluorophore, the fluorophore is incorporated within the sequence itself and is not configured to bind to a cellular component. A separate binding agent, an antibody, is used to achieve target binding. The fluorophore functions only as a detection label and does not participate in cellular binding or quantification.
These arguments are unpersuasive. The instant claims are drawn to a product and not a method of use as the restriction group drawn to the method of use was not elected in the response filed September 30, 2025. Therefore the claimed composition must be capable of being used for quantifying endogenous cellular components but the applied prior art need not explicitly teach such a use. The functions of a molecule cannot be separated from its structure. At least Hoechst dyes and calcein AM are configured to bind to an endogenous cellular component and the use of the fluorophores in the prior art not being identical does not patentably distinguish the instant claims. The nature of the conjugation between the oligonucleotide barcode and cellular dye is not further claimed. The cellular component-binding reagents disclosed by Nakamoto et al. can also comprise a cell membrane-permeable cellular component such as calcein AM, reasonably suggesting to one of ordinary skill in the art conjugation of such as fluorophore to the barcode (see p 13 of the November 4, 2025 Office Action for additional discussion).
Applicants also argue that the present invention is premised on a fundamentally different and non-suggested inventive concept of oligonucleotides being directly conjugated to cellular dyes and the construct used to encode and quantitatively measure endogenous cellular components across multiple sampled via sequencing. The remarks argue that in the present invention the oligonucleotide barcode is conjugated directly to a cellular or histological dye that serves as the primary quantitative reporter where in the sequencing readouts provide quantitative measurements of the targeted cellular components; the barcodes are attached to the small molecule dyes themselves enables multiplex staining of multiple cellular components and/or samples and sequencing based quantification using dyes rather than antibodies and both intracellular and non-protein cellular components [are] labeled by dyes and then quantified via sequencing of their associated barcoded dyes. The components measured in Nakamoto are primarily cell-surface or protein targets accessible to antibodies.
These arguments are unpersuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., direct fluorophore attachment and the fluorophore being the primary quantitative reporter) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The claims only require a fluorophore such as Hoechst or calcein AM that are capable of binding to endogenous cellular components being conjugated to a cellular dye. In the discussion of the scope of “endogenous cellular component” set forth on p 7 and 8 of the Remarks filed January 27, 2026 in response to indefiniteness rejections set forth in the November 4, 2025 Office Action, cell-surface or protein targets accessible to antibodies are not excluded from the scope of endogenous cell components. Explicit appreciation in the prior art of the ability of such fluorophores to bind to endogenous cellular components is not required as compositions having the claimed structure are disclosed by Nakamoto et al.
Applicants do not present any arguments regarding Zhu et al. or Cai et al. for the examiner to address herein.
Rejoinder of group II has not been considered as the claims of group I are not in condition for allowance.
Conclusion
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 Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618