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 .
Status of the Application
The Response to Final Office Action and the Request for Continued Examination, each filed April 22, 2026, are acknowledged.
Claims 11-12 and 14-29 were pending. Claims 11-12 and 14-25 are being examined on the merits. Claims 26-29 remain withdrawn.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 22, 2026 has been entered.
Response to Arguments
Applicant’s arguments filed April 22, 2026 have been fully considered.
The following rejections are WITHDRAWN in view of Applicant’s arguments and claim amendments:
Prior art rejections
The following rejections are MODIFIED in view of Applicant’s claim amendments:
Double patenting
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.
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 11-12 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Gingeras (US Patent App. Pub. No. 2005/0136412 A1) in view of Ji1 (Integrated parallel microfluidic device for simultaneous preparation of multiplex optical-encoded microbeads with distinct quantum dot barcodes, J Mater Chem, 21, 13380-13387, 2011) and Han2 (Quantum-Dot-Tagged Microbeads for Multiplexed Optical Coding of Biomolecules, Nat Biotechnol, 19, 631-635, 2001).
Regarding independent claim 11 and dependent claim 12, Gingeras teaches …
A method for optically encoding individual discrete volumes comprising: assigning
optically encoded particles, optionally a quantum dot, to individual discrete volumes, wherein a nucleic acid containing specimen of interest is loaded within the discrete volume and not attached to a surface (paras. 3-10; claims 1-2).
In addition, Ji teaches a set of optically encoded particles comprising distinct particles, and teaches that each distinct particle can be identified. Ji further teaches that the set of optically encoded particles comprises 2 to 500 distinct particles. That is, Ji teaches that the set of optically encoded particles comprises distinct particles, and teaches that each distinct particle can be identified (Fig. 6d; also see p. 13386, left col., para. 1: teaches two color barcoding with composite gradients of quantum dots, where the different quantum dots have fluorescent peaks that avoid spectral overlapping – thus Ji teaches at least two distinct particles).
Ji does not teach that each distinct particle comprises at least one nucleic acid particle identifier that identifies that distinct particle within the set of optically encoded particles. However, Han teaches this limitation. Specifically, Han teaches an embodiment with three optically encoded particles, each with a unique target-specific probe attached to the particle (Figs. 5-6; probes 1-4). Each particle type can thus be distinguished based on the sequence identity of the probe. Consequently, then the limitation requiring that an observable pattern of the distinct particles (i.e., the probes) within the set of optically encoded particles in each discrete volume allows each discrete volume to be independently identified (Figs. 5-6; probes 1-4).
Regarding dependent claims 14-15, Ji additionally teaches optically detecting a combination of optically-encoded particles delivered to each discrete volume, specifically capturing one or more images in one or more channels corresponding to the optically encoded particles (Figs. 4c, 6b, 6d), as recited in claims 14 and 15, respectively.
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Gingeras method to incorporate the Ji set of distinct particles and to detect the combination of those distinct particles. The ordinary artisan would have done so to achieve the expected advantage of a more efficient assay, as it would permit multiplex detection of different nucleic acid targets in the same reaction volume. The ordinary artisan would have had an expectation of success as the design and optimization of nucleic acid detection assays is well-known in the art.
It would have been additionally obvious to incorporate the unique nucleic acid particle identifiers of Han into the Gingeras plus Ji particles. Ji teaches that optical barcoding using fluorescence-encoded beads is useful for highly multiplexed detection of nucleic acids (e.g., gene expression). The ordinary artisan would have been motivated to incorporate unique nucleic acid particle identifiers into the Ji method in order to achieve the expected advantage of being able to incorporate an additional unique identifier into the assay which would improve the combinatorial coding and analysis capability even further. The ordinary artisan would have had an expectation of success as the design and optimization of nucleic acid detection assays is well-known in the art.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Gingeras (US Patent App. Pub. No. 2005/0136412 A1) in view of Ji (Integrated parallel microfluidic device for simultaneous preparation of multiplex optical-encoded microbeads with distinct quantum dot barcodes, J Mater Chem, 21, 13380-13387, 2011) and Han (Quantum-Dot-Tagged Microbeads for Multiplexed Optical Coding of Biomolecules, Nat Biotechnol, 19, 631-635, 2001) as applied to claim 11 above, and further in view of Bharadwaj3 (US Patent App. Pub. No. 2015/0292988).
Regarding dependent claim 16, Gingeras teaches hybridizing one or more antisense
oligonucleotides to one or more target sequences in the nucleic acid containing specimen (paras. 3, 10, 54). Bharadwaj teaches that the oligonucleotide is a primer (para. 33).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to further modify the modified Gingeras method, discussed above, to incorporate the primer of Bharadwaj. Ji teaches that optical barcoding using fluorescence-encoded beads is useful for highly multiplexed detection of nucleic acids (e.g., gene expression). The ordinary artisan would have been additionally motivated to incorporate a primer into this method in order to achieve the expected advantage of being able to incorporate an additional sequence into the target nucleic acid amplicon (e.g., using a primer comprising a barcode to incorporate a barcode into the amplicon) which would improve the combinatorial coding and analysis capability even further. The ordinary artisan would have had an expectation of success as the design and optimization of nucleic acid detection assays is well-known in the art.
Claims 17-25 are rejected under 35 U.S.C. 103 as being unpatentable over Gingeras (US Patent App. Pub. No. 2005/0136412 A1) in view of Ji (Integrated parallel microfluidic device for simultaneous preparation of multiplex optical-encoded microbeads with distinct quantum dot barcodes, J Mater Chem, 21, 13380-13387, 2011) and Han (Quantum-Dot-Tagged Microbeads for Multiplexed Optical Coding of Biomolecules, Nat Biotechnol, 19, 631-635, 2001).
Regarding independent claim 17 and dependent claim 18, Gingeras teaches …
A method for optically encoding individual discrete volumes comprising: distributing
optically encoded particles, optionally a quantum dot, to individual discrete volumes, wherein a nucleic acid containing specimen of interest is loaded within the discrete volume and not attached to a surface (paras. 3-10; claims 1-2).
In addition, Ji teaches a set of optically encoded particles comprising distinct particles, and teaches that each distinct particle can be identified. Ji further teaches that the set of optically encoded particles comprises 2 to 500 distinct particles. That is, Ji teaches that the set of optically encoded particles comprises distinct particles, and teaches that each distinct particle can be identified (Fig. 6d; also see p. 13386, left col., para. 1: teaches two color barcoding with composite gradients of quantum dots, where the different quantum dots have fluorescent peaks that avoid spectral overlapping – thus Ji teaches at least two distinct particles).
Gingeras and Ji do not teach associating the particles with optically-labeled nucleic
acids, thereby generating optically encoded particles. However, Han suggests this limitation, and specifically teaches that the nucleic acids are probes (Fig. 5). Specifically, Han teaches an embodiment with three optically encoded particles, each with a unique target-specific probe attached to the particle (Figs. 5-6; probes 1-4). Each particle type can thus be distinguished based on the sequence identity of the probe. Han also teaches labeling DNA molecules directly with a fluorescent dye (p. 634, right col., para. 1).
Regarding dependent claims 22-23, Ji additionally teaches optically detecting a combination of optically-encoded particles delivered to each discrete volume, specifically capturing one or more images in one or more channels corresponding to the optically encoded particles (Figs. 4c, 6b, 6d), as recited in claims 22 and 23, respectively.
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Gingeras method to incorporate the Ji set of distinct particles and to detect the combination of those distinct particles. The ordinary artisan would have done so to achieve the expected advantage of a more efficient assay, as it would permit multiplex detection of different nucleic acid targets in the same reaction volume. The ordinary artisan would have had an expectation of success as the design and optimization of nucleic acid detection assays is well-known in the art.
It would have been additionally obvious to incorporate the unique nucleic acid particle identifiers of Han into the Gingeras plus Ji particles. Ji teaches that optical barcoding using fluorescence-encoded beads is useful for highly multiplexed detection of nucleic acids (e.g., gene expression). The ordinary artisan would have been motivated to incorporate unique nucleic acid particle identifiers into the Ji method in order to achieve the expected advantage of being able to incorporate an additional unique identifier into the assay which would improve the combinatorial coding and analysis capability even further. The ordinary artisan would have had an expectation of success as the design and optimization of nucleic acid detection assays is well-known in the art.
Regarding dependent claim 19, Ji also teaches that the set of optically encoded particles comprises distinct types of particles, and teaches that each distinct type of particle within the set can be uniquely identified (Fig. 6d), but Ji does not teach that each distinct type of particle within the set of optically encoded particles comprises at least one unique nucleic acid particle identifier that identifies that distinct particle type within the set of optically encoded particles. However, Han teaches this limitation. Specifically, Han teaches an embodiment with three optically encoded particles, each with a unique target-specific probe attached to the particle (Figs. 5-6; probes 1-4). Each particle type can thus be distinguished based on the sequence identity of the probe. Consequently, then the limitation requiring that the observable pattern of the one or more nucleic acid particle identifier of each distinct type of particle (i.e., the probes) within the set of optically encoded particles in each discrete volume allows each discrete volume to be independently identified (Figs. 5-6; probes 1-4).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to further modify the modified Gingeras method, discussed above, to incorporate the unique nucleic acid particle identifiers of Han. Ji teaches that optical barcoding using fluorescence-encoded beads is useful for highly multiplexed detection of nucleic acids (e.g., gene expression). The ordinary artisan would have been motivated to incorporate unique nucleic acid particle identifiers into the Ji method in order to achieve the expected advantage of being able to incorporate an additional unique identifier into the assay which would improve the combinatorial coding and analysis capability even further. The ordinary artisan would have had an expectation of success as the design and optimization of nucleic acid detection assays is well-known in the art.
Regarding dependent claims 20-21 and 24, Han teaches or suggests mixing functionalized particles with optically-labeled nucleic acids, and annealing the mixture (Figs. 5-6; probes 1-4; p. 634, right col., para. 1), as recited in claim 20. Ji and Han both teach using distinct ratios of one or more optical labels (Ji: Figs. 5-6; p. 13382, right col., para. 2; p. 13386, left col., para. 1; Han: Figs. 5-6; abstract; p. 633, right col., para. 2), as recited in claim 21. Finally, Ji teaches that the particle is a hydrogel (p. 13381, left col., para. 3 through right col., para. 1), as recited in claim 24.
Regarding dependent claim 25, Han teaches hybridizing the labeled nucleic acids
(specifically, a probe) to one or more target sequences in the nucleic acid containing species (Fig. 5).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to further modify the modified Gingeras method, discussed above, to incorporate the annealing steps and unique probe of Han. Ji teaches that optical barcoding using fluorescence-encoded beads is useful for highly multiplexed detection of nucleic acids (e.g., gene expression). The ordinary artisan would have been additionally motivated to incorporate a unique probe into this method in order to achieve the expected advantage of being able to incorporate an additional unique identifier into the assay which would improve the combinatorial coding and analysis capability even further. The ordinary artisan would have had an expectation of success as the design and optimization of nucleic acid detection assays is well-known in the art.
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.
Claims 11-12, 14-19, 22-23 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 13, 16 and 19 of U.S. Patent No. 11,421,270 (hereinafter, the ‘270 patent).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 16 and 19 of the ’270 patent teaches all of the limitations of instant claims 11 and 17, although in different embodiments. More specifically, claim 1 of the ’270 patent is directed to a method for multiplex screening of nucleic acid sequence variations comprising, in part, dispensing a solution comprising a set of optically-encoded particles to one or more discrete volumes, each of which also comprises a sample with target nucleic acids. The optically-encoded particles each have one or more primers of a same primer type associated with them. Each primer of the same primer type has a particle identifier that identifies the type of optically-encoded particle.
Instant independent claims 11 and 17 are directed to a method for optically encoding individual discrete volumes, using a set of optically-encoded particles, as with claim 1 of the ‘270 patent. Instant claim 11 also requires distinct types of optically-encoded particles where each comprises at least one unique nucleic acid particle identifier (e.g., a primer), where the pattern of the at least one unique identifier in each discrete volume allows that discrete volume to be independently identified. Thus, the instant claims 11 and 17 method of optically encoding individual discrete volumes are embodiments comprised within the “dispensing” clause of the ‘270 patent claim 1 method for multiplex screening of nucleic acid sequence variations.
In addition, claims 13, 1, 2, 1, 13, 1, 1, 2 and 1 of the ‘270 patent teach all of the limitations of instant claims 12, 14, 15, 16, 18, 19, 22, 23 and 25, respectively.
Modifying the ‘270 patent embodiments by re-arranging method steps to create different embodiments of the step of optically encoding individual discrete volumes would have been prima facie obvious to the ordinary artisan, as they would have been motivated to optimize the embodiment through routine experimentation to customize the embodiment as desired for a particular assay. The ordinary artisan would have had an expectation of success as nucleic acid assay design is well-known in the art. Thus, instant claims 12-16, 18, 19, 22-23 and 25 are not patentably distinct from claims 1-2 and 13 of the ‘270 patent.
Conclusion
Claims 11-12 and 14-25 are being examined, and are rejected. No claims are allowed.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 Ji was cited in the PTO-892 Notice of References Cited mailed March 27, 2024.
2 Han was cited in the PTO-892 Notice of References Cited mailed March 27, 2024.
3 Bharadwaj was cited in the Information Disclosure Statement submitted November 30, 2022.
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