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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 February 05, 2026 has been entered.
Applicant previously canceled claims 2-4, 17-23, and 28-71. Claims 1, 5-16 and 24-27 are currently pending and under examination.
Any objection or rejection of record in the previous Office Action, which is not addressed in this action has been withdrawn in light of Applicant’s amendments and/or arguments.
Claim Rejections - 35 USC § 102
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 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.
Claims 1, 4-9, 11-12, 14 and 16 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Hindson et al. (U.S Patent Application Publication US 2014/0378322 A1, published December 25, 2014), previously cited in the November 06, 2025 Office Action. This rejection is maintained and modified as necessitated by amendments.
Regarding claim 1, Hindson teaches a method of barcoding nucleic acids of a particle (Page 30, [0245]-[0246], Page 1, [0006] and Page 56, [0429]). Hindson teaches combining a fluid sample with a magnetic capture bead (Page 29, [0238], Page 21, [0188] and Page 28, [0232]). Hindson teaches a capture moiety for the particle of the sample and a barcode nucleic acid comprising a target binding region to produce a captured sample (Page 29, [0241], Page 30, [0245]-[0246] and Page 22, [0194]). Hindson teaches partitioning captured particles of the captured sample into microwells, using an applied magnetic field mediated partitioning protocol to produce partitioned captured particles (Page 20, [0180], Page 23, [0198], Page 28, [0232], Page 29, [0238], Page 29, [0240], Page 54, [0413], ). Hindson teaches lysing the partitioned captured particles so that nucleic acids released therefrom bind to the target binding regions of the bead bound barcode nucleic acids to produce captured nucleic acids (Page 30, [0246] and Page 56, [0429]).
Regarding claim 5, Hindson teaches the capture moiety comprises a specific binding member (Page 29, [0241] and Page 30, [0246]).
Regarding claim 6, Hindson teaches the specific binding member comprises an antibody or binding fragment thereof (Page 29, [0241] and Page 30, [0246]).
Regarding claim 7, Hindson teaches the bead bound barcode nucleic acids further comprise a cell label domain (Page 18, [0167], Page 30, [0246] and Page 56, [0430]).
Regarding claim 8, Hindson teaches the bead bound barcode nucleic acids further comprise a unique molecular index domain (Page 18, [0163], Page 18, [0167] and Page 58, [0439]).
Regarding claim 9, Hindson teaches the bead bound barcode nucleic acids further comprise a universal primer binding domain (Page 3, [0017], Pages 15-16, [0148]-[0151] and Page 29, [0235]).
Regarding claim 11, Hindson teaches the target binding region comprises a gene specific domain or a random sequence domain (Page 2, [0013], Page 3, [0023], Page 8, [0096], Page 47, [0358]-[0359], Page 48, [0364] and Page 49, [0368]).
Regarding claim 12, Hindson teaches the particle comprises a sub-cellular sized particle (Page 30, [0245], Pages 31-32, [0252] and Page 56, [0429]).
Regarding claim 14, Hindson teaches the particle comprises a cell (Page 10, [0102], Page 30, [0246] and Page 56, [0429]-[0430]).
Regarding claim 16, Hindson teaches the separating comprises employing an applied magnetic field (Page 20, [0180], Page 23, [0198], Page 28, [0232] and Page 29, [0238]).
Hindson teaches each and every limitation of claims 1, 5-9, 11-12, 14 and 16, and therefore, Hindson anticipates claims 1, 5-9, 11-12, 14 and 16.
Claims 1, 5-6, 8-9, 11-12, 14-16, 24-25 and 27 are rejected under 35 U.S.C. 102 (a)(1) and 102 (a)(2) as being anticipated by Salathia et al. (U.S Patent Application Publication US 2016/0053253 A1, published February 25, 2016), cited on the IDS filed October 05, 2023. This is a new rejection.
Regarding claim 1, Salathia teaches a method of barcoding nucleic acids of a particle (Page 1, [0007], Page 3, [0045], Page 4, [0062] and Page 5, [0070] and [0072]). Salathia teaches combining a fluid sample with a magnetic capture bead (Page 2, [0017], Page 8, [0093], Pages 8-10, [0095], Pages 10-12, [0097]-[0099], Page 12-13, [0101]-[0103] and [0105] and Pages 14-15, [0114]). Salathia teaches a capture moiety for the particle of the sample (Page 2, [0015], Page 3, [0032]-[0033], Pages 10-11, [0097] and Pages 11-12, [0099]). Salathia teaches a barcode nucleic acid comprising a target binding region to produce a captured sample (Page 6, [0076], Page 1, [0008]-[0010], Page 3, [0032]-[0033], [0037] and [0039], and Page 4, [0064]). Salathia teaches partitioning captured particles of the captured sample into microwells using an applied magnetic field mediated partitioning protocol to produce partitioned captured particles (Pages 8-10, [0095] and Pages 10-11, [0097] and Page 12-13, [0101]-[0103] and [0105]). Salathia teaches lysing the partitioned captured particles so that nucleic acids released therefrom bind to the target binding regions of the bead bound barcode nucleic acids to produce captured nucleic acids (Page 5, [0072], Page 8, [0093] and Page 14, [0110]).
Regarding claim 5, Salathia teaches the capture moiety comprises a specific binding member (Page 2, [0015], Page 3, [0032]-[0033], Pages 10-11, [0097] and Pages 11-12, [0099]).
Regarding claim 6, Salathia teaches the specific binding member comprises an antibody or binding fragment thereof (Page 2, [0015], Page 3, [0032]-[0033], Pages 10-11, [0097] and Pages 11-12, [0099]).
Regarding claim 8, Salathia teaches the bead bound barcode nucleic acids further comprise a unique molecular index domain (Page 1, [0008], Page 2, [0012] and [0019] and Page 3, [0037] and [0039]).
Regarding claim 9, Salathia teaches the bead bound barcode nucleic acids further comprise a universal primer binding domain (Page 1, [0008] and Pages 7-8, [0092]).
Regarding claim 11, Salathia teaches the target binding region comprises an oligo dT domain, a gene specific domain or a random sequence domain (Page 5, [0072], Page 8, [0093] and Page 14, [0110]).
Regarding claim 12, Salathia teaches the particle comprises a sub- cellular sized particle (Page 1, [0007] and [0009], Page 2, [0013] and Pages 11-12, [0099]).
Regarding claim 14, Salathia teaches the particle comprises a cell (Page 1, [0007], Page 3, [0045], Page 4, [0062] and Page 5, [0070] and [0072]).
Regarding claim 15, Salathia teaches the method further comprises separating captured nucleic acids from other constituents of the partitioned captured particles (Page 1, [0010] and Page 3, [0032]-[0034]).
Regarding claim 16, Salathia teaches the separating comprises employing an applied magnetic field (Page 1, [0010], Page 3, [0032]-[0034], Pages 8-10, [0095] and Pages 10-11, [0097]).
Regarding claim 24, Salathia teaches a method of sequencing nucleic acids of a particle (Page 1, [0007] and Page 2, [0013]). Salathia teaches combining a fluid sample containing the particle with a magnetic capture bead (Page 2, [0017], Page 8, [0093], Pages 8-10, [0095], Pages 10-12, [0097]-[0099], Page 12-13, [0101]-[0103] and [0105] and Pages 14-15, [0114]). Salathia teaches barcode nucleic acids comprising a target binding region (Page 6, [0076], Page 1, [0008]-[0010], Page 3, [0032]-[0033], [0037] and [0039], and Page 4, [0064]). Salathia teaches a capture moiety that specifically binds to the particle to produce a captured sample (Page 2, [0015], Page 3, [0032]-[0033], Pages 10-11, [0097] and Pages 11-12, [0099]). Salathia teaches partitioning captured particles of the captured sample into microwells using an applied magnetic field mediated partitioning protocol to produce partitioned captured particles (Pages 8-10, [0095] and Pages 10-11, [0097] and Page 12-13, [0101]-[0103] and [0105]). Salathia teaches lysing the partitioned captured particles so that nucleic acids released therefrom bind to target binding regions of the barcode nucleic acids to produce captured nucleic acids (Page 5, [0072], Page 8, [0093] and Page 14, [0110]). Salathia teaches subjecting the captured nucleic acids to cDNA synthesis reaction conditions to produce first strand cDNA domain comprising capture nucleic acids (Page 1, [0009]-[0010], Page 2, [0012]-[0014] and [0017] and Page 4, [0059], [0061] and [0066], ). Salathia teaches producing a NGS library from the first strand cDNA domain comprising capture nucleic acids (Page 1, [0005] and [0009]-[0010], Page 2, [0012]-[0014] and [0017], Page 4, [0061]-[0063] and Claim 1). Salathia teaches sequencing the Next Generation Sequencing (NGS) library to sequence nucleic acids of the target particle (Page 1, [0005] and [0009]-[0010], Page 2, [0012]-[0014] and [0017] and Page 4, [0061]-[0063]).
Regarding claim 25, Salathia teaches the particle comprises a sub-cellular sized particle (Page 1, [0007] and [0009], Page 2, [0013] and Pages 11-12, [0099]).
Regarding claim 27, Salathia teaches the particle comprises a cell (Page 1, [0007], Page 3, [0045], Page 4, [0062] and Page 5, [0070] and [0072]).
Salathia teaches each and every claim limitation of claims 1, 5-6, 8-9, 11-12 and 14-16, therefore Salathia anticipates claims 1, 5-6, 8-9, 11-12, 14-16, 24-25 and 27
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.
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 10 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Hindson et al. (U.S Patent Application Publication US 2014/0378322 A1, published December 25, 2014), as applied to claims 1, 5-9, 11-12, 14 and 16 above, in view of Betts et al. (U.S Patent Application Publication US 2017/0073730 A1, published March 16, 2017), previously cited in the Office action filed November 15, 2024. This rejection is maintained and modified as necessitated by amendments.
Regarding claim 10, Hindson teaches the bead bound barcodes as discussed above.
Regarding claim 15, Hindson teaches the partitioned captured particles as discussed above.
Hindson does not expressly teach or suggest the bead bound barcode nucleic acids comprise the following structure: bead-5'-universal primer binding domain-cell label domain-unique molecular index domain-target binding region-3'. Hindson does not teach or suggest separating captured nucleic acids from other constituents of the partitioned captured particles.
Betts teaches barcoding and capturing nucleic acids (Fig. 2). Betts teaches the bead bound barcode nucleic acids comprise the following structure: bead-5'-universal primer binding domain-cell label domain-unique molecular index domain-target binding region-3' (Fig. 2). Betts teaches separating captured nucleic acids from other constituents of the partitioned captured cells (Page 11, [0069] and [0078], and Page 22, [0168]). Betts teaches that using the exemplary embodiment of the stochastic barcoding method (specific structure: bead-5'-universal primer binding domain-cell label domain-unique molecular index domain-target binding region-3') allows for indexing of individual nucleic acid molecules with unique barcodes so that molecules of specific targets can be tracked and/or counted (Page 21, [0159]-[0160] and Fig. 2)
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Hindson with the teachings of Betts to include separating captured nucleic acids from other constituents of the partitioned captured cells as well as use the specific structure bead-5'-universal primer binding domain-cell label domain-unique molecular index domain-target binding region-3'. This would allow for indexing of individual nucleic acid molecules with unique barcodes so that molecules of specific targets can be tracked and/or counted, as taught by Betts (Page 21, [0159]-[0160] and Fig. 2).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Hindson et al. (U.S Patent Application Publication US 2014/0378322 A1, published December 25, 2014), as applied to claims 1, 5-9, 11-12, 14 and 16 above, in view of Routenberg et al. (WIPO International Patent Application Publication WO 2019/222708 A2, published November 21, 2019). This rejection is maintained and modified as necessitated by amendments.
Regarding claims 13, Hindson teaches the particle as discussed above.
Hindson does not teach or suggest the sub-cellular sized particle is specifically a vesicle.
Routenberg teaches capturing nucleic acids isolated in extracellular vesicles (EV) (Page 4, [0011]). Routenberg teaches using magnetic beads and allowing for collection of particles using an applied magnetic field (Page 31, [00127], Page 45, [00145]). Routenberg teaches capturing EVs with a capture moiety on the surface of a magnetic bead (i.e., capturing a particle that is sub-cellular as well as a vesicle, Page 45 [00415] and Figs. 32-33). Routenberg teaches the magnetic bead may have an additional barcode sequence separate from the capture moiety (Fig. 32-33). Routenberg teaches using these methods allows for highly specific isolation and analysis of extracellular vesicles (EVs) as well performing multiplexed methods of comparing different EVs in the same sample, reducing the amount of sample required and decrease sample-to-sample variability (Abstract and Page 58, [00227]-[00228]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teaching of Hindson with the teachings of Routenberg using a particle comprises a sub-cellular sized particle, specifically a vesicle. This would allow for highly specific isolation and analysis of extracellular vesicles (EVs) as well performing multiplexed methods of comparing different EVs in the same sample, reducing the amount of sample required and decrease sample-to-sample variability as taught by Routenberg (Abstract and Page 58, [00227]-[00228]).
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Salathia et al. (U.S Patent Application Publication US 2016/0053253 A1, published February 25, 2016), cited on the IDS filed October 05, 2023, as applied to claims 1, 5-6, 8-9, 11-12, 14-16, 24-25 and 27 above, in view of Routenberg et al. (WIPO International Patent Application Publication WO 2019/222708 A2, published November 21, 2019), previously cited in the November 06, 2025 Office Action. This is a new rejection as necessitated by amendments.
Regarding claims 26, Salathia teaches the sub-cellular sized particle as discussed above.
Salathia does not teach or suggest the sub-cellular sized particle is specifically a vesicle.
Routenberg teaches capturing nucleic acids isolated in extracellular vesicles (EV) (Page 4, [0011]). Routenberg teaches using magnetic beads and allowing for collection of particles using an applied magnetic field (Page 31, [00127], Page 45, [00145]). Routenberg teaches capturing EVs with a capture moiety on the surface of a magnetic bead (i.e., capturing a particle that is sub-cellular as well as a vesicle, Page 45 [00415] and Figs. 32-33). Routenberg teaches the magnetic bead may have an additional barcode sequence separate from the capture moiety (Fig. 32-33). Routenberg teaches using these methods allows for highly specific isolation and analysis of extracellular vesicles (EVs) as well performing multiplexed methods of comparing different EVs in the same sample, reducing the amount of sample required and decrease sample-to-sample variability (Abstract and Page 58, [00227]-[00228]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teaching of Salathia with the teachings of Routenberg using a particle comprises a sub-cellular sized particle, specifically a vesicle. This would allow for highly specific isolation and analysis of extracellular vesicles (EVs) as well performing multiplexed methods of comparing different EVs in the same sample, reducing the amount of sample required and decrease sample-to-sample variability as taught by Routenberg (Abstract and Page 58, [00227]-[00228]).
Response to Arguments
Applicant’s arguments and amendments, filed December 22, 2025 regarding the rejections of claims 24 and 27 under 35 U.S.C. § 102 have been fully considered and are deemed to be persuasive. Therefore, these rejections are withdrawn.
Applicant’s arguments and amendments, filed December 22, 2025 regarding the rejections of claims 25 and 26 under 35 U.S.C. § 103 have been fully considered and are deemed to be persuasive. Therefore, these rejections are withdrawn.
Applicant’s arguments and amendments, filed December 22, 2025 regarding the rejections of claims 1, 4-9, 11-12, 14 and 16 under 35 U.S.C. § 102 have been fully considered but they are not persuasive.
Applicant asserts that as “Hindson applies magnetic separation to beads ‘already comprising amplified template oligonucleotides’, Hindson fails to teach partitioning any captured particles using an applied magnetic field, much less partitioning captured particles into microwells using an applied magnetic field” as well as, “nucleic acids are only available to be amplified after partitioning the captured particles into microwells and lysing the particles”. However, it is noted that this is not a claim limitation, and the claims do not make any mention of amplification and it is not proper to import claim limitations from the specification into the claims. “Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Additionally, applicant asserts “paragraphs [0198] and [0232] of Hindson are directed to magnetic separation of beads that occurs after thermal cycling and magnetic separation of beads that occurs after PCR, respectively. In other words, Hindson's method is used to separate beads comprising amplified nucleic acids”, as reiterated above, the claims make no mention of amplification or amplified nucleic acids or lacking amplified nucleic acids in the partitioning protocol. Hindson [0198] discloses “beads may be pooled into a common vessel (e.g., partitioned in microwell) [by] magnetic separation…then subject to additional rounds of bulk processing if desired”. Hindson further discloses in [0413] that a vessel/partition may be a microwell. Hindson [0232] discloses “barcoded beads suspended in aqueous solution may be sorted by magnetic separation or other sorting methods to obtain a collection of purified barcoded beads in aqueous fluid”. Additionally, Hindson in [0240] discloses “A capture device, such as a magnetic bead, with a corresponding linkage, such as streptavidin, may be added to bind the capture moiety, for example, biotin. The attached magnetic bead may then enable isolation of the barcoded beads by, for example, magnetic sorting”. Moreover, Hindson in [0180], discloses “contents of the partitions may be pooled into a common vessel (e.g., a tube, a well, etc.). The beads comprising the amplified template oligonucleotides may then be separated from the other contents of the partitions (including beads that do not comprise amplified template oligonucleotides) by any suitable method including, for example, centrifugation and magnetic separation, with or without the aid of a capture moiety as described elsewhere herein”. Therefore, Hindson does in fact disclose partitioning captured particles into microwells using an applied magnetic field mediated partitioning protocol and this rejection is maintained as set forth above.
Applicant’s arguments and amendments, filed December 22, 2025 regarding the rejections of claims 10 and 15 under 35 U.S.C. § 103 have been fully considered but they are not persuasive.
Applicant additionally asserts “Hindson fails to teach the element of partitioning captured particles of the captured sample into microwells using an applied magnetic field mediated partitioning protocol … [and] Betts fails to make up for the deficiencies in Hindson”. As discussed above, Hindson does in fact disclose this feature and the rejection is maintained as set forth above.
Applicant’s arguments and amendments, filed December 22, 2025 regarding the rejection of claim 13 under 35 U.S.C. § 103 have been fully considered but they are not persuasive.
Applicant additionally asserts “Hindson fails to teach the element of partitioning captured particles of the captured sample into microwells using an applied magnetic field mediated partitioning protocol … [and] Routenberg fails to make up for the deficiencies in Hindson”. As discussed above, Hindson does in fact disclose this feature and the rejection is maintained as set forth above.
Additionally, as discussed above, newly cited Salathia discloses a method of barcoding and sequencing nucleic acids of a particle, comprising combining a fluid sample with a magnetic capture bead and a capture moiety for the particle of the sample. Salathia discloses a barcode nucleic acid comprising a target binding region to produce a captured sample as well as partitioning captured particles of the captured sample into microwells using an applied magnetic field mediated partitioning protocol to produce partitioned captured particles.
Therefore, for all these reasons and those listed above, Hindson, Salathia, Hindson in view of Betts, Hindson in view of Routenberg, and Salathia in view of Routenberg are deemed to render the instant invention anticipated/obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684