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 .
DETAILED ACTION
Pursuant to a preliminary amendment filed May 5, 2026 claims 1-21 are currently pending in the instant application.
Response to Election/Restriction
Applicant's election of Group I, claims 1 and 5, directed to a method of preparing an immobilized library of tagged fragments from a sample comprising RNA and DNA; and the election of Species as follows:
Species (A): Applicant failed to elect one of (a) to (c) (claim 5), in the reply filed May 5, 2026 is acknowledged.
Claims 2-4 and 6-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1 and 5 are under consideration to which the following grounds of rejection are applicable.
Interview Summary
The Examiner contacted the Applicant’s representative Michael McClain on May 12, 2026 to request a telephonic election for Species (A) in the Requirement for Election/Restriction mailed March 5, 2026. The Examiner left a message. No telephonic species election was subsequently provided.
Priority
The present application filed February 2, 2023 is a CON of 35 U.S.C. 371 national stage filing of International Application PCT/US21/44715, filed August 5, 2021, which claims the benefit US Provisional Patent Applications 63219014, filed July 7, 2021; 63168802, filed March 31, 2021; 63165830, filed March 25, 2021; and 63061885, filed August 6, 2020.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application 63168802, filed March 31, 2021, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific method steps recited in independent claim 1 does not have support for; combining a sample comprising RNA and DNA with a first solid support” and “combining a sample with a second solid support for immobilizing cDNA”; and “immobilizing the cDNA”. Therefore, the priority date for the presently claimed invention is July 7, 2021, the filing date of US Provisional Patent Application 63219014.
Applicants are invited to specifically indicate the location of the cited phrase pertinent to claim 1 of the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 24, 2025 has been considered. An initialed copy of the IDS accompanies this Office Action.
Claim Objections/Rejections
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 5 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 is indefinite for the recitation of the terms “combining the sample with a second solid support” such as recited in claim 1, line 12 because it is unclear what nucleic acids are present in the sample as recited in step (e). It is unclear whether: (i) the DNA has been removed from the sample following step (c); (ii) whether “the sample” as recited in (e) still comprises both RNA and DNA (line 4); or (iii) the sample of step (d) only comprises cDNA. Moreover, it is unclear whether the “combining” in (a) and the “combining” in (e) are performed simultaneously, sequentially, separately, or by some other method and, thus, the metes and bounds of the claim cannot be determined.
Claim 5 is indefinite for the recitation of the term “different primer binding sequences” such as recited in claim 5, line 2 because claim 5 depends from instant claim 1, wherein claim 1 does not recite that the DNA-specific barcode or the RNA-specific barcode comprise a primer binding sequence and, thus, the metes and bounds of the claim cannot be determined.
Claim 5 is indefinite for the recitation of the term “optionally” such as recited in claim 5, line 2 because it is unclear whether any of the steps (a)-(c) occur and, thus, the metes and bounds of the claim cannot be determined.
Claim 5 is indefinite for the recitation of the term “the primer binding sequence” such as recited in claim 5, lines 5, 7, 10 and 11. There is insufficient antecedent basis for the term “the primer binding sequence” in the claim because claim 5, line 2 recites the term “different primer binding sequences.” The Examiner suggests that Applicant amend the claim to recite, for example, “a primer that binds the different primer binding sequences comprised in the DNA-specific barcode.”
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 5 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 5 recites (in part): “wherein the DNA-specific barcode and the RNA-specific barcode comprise different primer binding sequences” in lines 1-2 because claim 5 depends from instant claim 1, wherein claim 1 does not recite that the DNA-specific barcode or the RNA-specific barcode comprise a primer binding sequence. Thus, claim 5 is an improper dependent claims for failing to further limit the subject matter of the claim upon which they depend, or for failing to include all the limitations of the claim upon which they depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 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 and 5 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Gormley et al. (hereinafter “Gormley”) (US Patent Application Publication No. 20140194324, published July 10, 2014).
Regarding claim 1, Gormley teaches that the step of applying a target DNA comprises adding a biological sample to a solid support, wherein the biological sample can be any type that comprises DNA and which can be deposited onto the solid surface for tagmentation, wherein the biological sample comprises a mixture of DNA, protein, other nucleic acid species, other cellular components and/or any other contaminant present in approximately the same proportion as found in vivo (interpreted as combining a sample comprising DNA and RNA with a solid support, claim 1a) (paragraph [0062], lines 1-5 and 11-13). Gormley teaches methods and compositions useful for generating libraries of tagged DNA fragments for use, such as in next generation sequencing methods, and the like, wherein the invention relates to preparation of linear ssDNA fragments on a solid support from target DNA comprising any dsDNA of interest (including double-stranded cDNA prepared from RNA), from any source, for genomic, sub genomic, transcriptomic, or meta genomic analysis, or analysis of RNA expression (interpreted as preparing libraries of tagged fragments; sample comprising DNA and RNA; and preparing cDNA from RNA, claim 1) (paragraph [0004]). Gormley teaches that the method of preparing an immobilized library of tagged DNA fragments comprising: (a) providing a solid support having transposome complexes immobilized thereon (interpreted as a first and second solid support comprising transposome complexes immobilized thereon, claim 1a,e), wherein the transposome complexes comprise a transposase bound to a first polynucleotide, the first polynucleotide comprising (i) a 3' portion comprising a transposon end sequence, and (ii) a first tag comprising a first tag domain; and (b) applying a target DNA to the solid support under conditions whereby the target DNA is fragmented by the transposome complexes, and the 3' transposon end sequence of the first polynucleotide is transferred to a 5' end of at least one strand of the fragments; thereby producing an immobilized library of double-stranded fragments wherein at least one strand is 5'-tagged with the first tag including wherein the transposome complexes comprise a second polynucleotide comprising a region complementary to said transposon end sequence; and that the methods can further comprise (c) providing transposome complexes in solution and contacting the transposome complexes with the immobilized fragments under conditions whereby the target DNA is fragmented by the transposome complexes in solution; thereby obtaining immobilized nucleic acid fragments having one end in solution, such that the transposome complexes in solution can comprise a second tag, such that the method generates immobilized nucleic acid fragments having a second tag, the second tag in solution, wherein the first and second tags can be different or the same (interpreted as combining a sample with a first solid support and a second solid support comprising transposome complexes; immobilizing DNA; immobilizing cDNA; and comprising a DNA-specific barcode and an RNA-specific barcode, claims 1b, 1e and 1f) (paragraph [0005]). Gormley teaches that the barcoding method comprises providing a population of microparticles having transposome complexes immobilized thereto, the transposome complexes comprising a transposase bound to a first polynucleotide and second polynucleotide, such that the first polynucleotide comprises an index domain associated with the microparticle, wherein the index domain can be unique to the microparticle; and/or the population of microparticles comprises at least a plurality of index domains (interpreted as DNA-specific barcodes and RNA-specific barcodes, claim 1) (paragraph [0113]). Gormley teaches that the barcoding methods presented further comprise applying a target DNA to the population of microparticles, thereby generating immobilized DNA fragments that are tagged with the index domain, wherein DNA can be efficiently contacted with surface bound transposomes using any suitable method for increasing the probability of contact as discussed hereinabove, as exemplified by the incorporated materials Of WO 2010/115122 (interpreted as DNA-specific barcodes and RNA-specific barcodes, claim 1) (paragraph [0114]). Gormley teaches that Figure 2a illustrates a tagmentation reaction, wherein addition of DNA to the flowcell results in tagmentation and coupling of the DNA to the transposomes (interpreted as performing a tagmentation reaction, claim 1c,f) (paragraphs [0017]; [0019]; and Figures 2a and 3a).
Regarding claim 5, Gormley teaches that Figures 9-12 provide an illustration of transposomes assembled on the surface of paramagnetic beads, such that Figure 9 shows a bead surface with two different first polynucleotides immobilized thereto, wherein the first polynucleotides that are shown comprise a transposon end sequence (ME), such that one of the first polynucleotides shown in comprises a tag domain comprising an amplification primer sequence (P5) and a sequencing primer sequence (Read 1); and the other polynucleotide shown in Figure 9 comprises a different amplification primer sequence (P7) and a sequencing primer sequence (Read 2), wherein the first polynucleotides can also comprise an index tag, such that the index tag can be unique to the bead, or it can be shared with one or more other beads in the population, wherein a single bead can have only a single index tag immobilized thereto, or it can have a plurality of index tags immobilized thereto (interpreted as DNA-specific and RNA-specific barcodes; barcodes comprising different primer binding sequences; and amplifying tagged fragments using a primer that binds the primer binding sequence, claim 5) (paragraph [0102]; and Figures 9-12). Figure 9 is shown below:
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Gormley teaches that the methods, immobilizing comprises: (a) providing a solid support having amplification primers coupled thereto; (b) hybridizing a second polynucleotide to one of the amplification primers, the second oligonucleotide comprising a region complementary to a transposon end sequence and a region complementary to the first tag (interpreted as a barcode comprising a primer binding sequence); (c) extending the amplification primer using a polymerase to generate a duplex comprising the first polynucleotide hybridized to the second polynucleotide, the first polynucleotide immobilized directly to the solid support (interpreted as amplifying); and (d) contacting the solid support with transposase holoenzyme, thereby assembling a transposome complex on the solid support (interpreted as barcodes comprising different primer binding sequences; and amplifying tagged fragments using a primer that binds the primer binding sequence, claim 5) (paragraph [0008]). Gormley teaches that any of the amplification methodologies described herein or generally known in the art can be utilized with universal or target-specific primers to amplify immobilized DNA fragments, wherein suitable methods for amplification include, but are not limited to, the polymerase chain reaction (PCR), strand displacement amplification (SDA), transcription mediated amplification (IMA) and nucleic acid sequence based amplification (NASBA) (interpreted as amplifying tagged fragments comprising the DNA-specific barcodes and/or RNA-specific barcodes, claim 5) (paragraph [0079], lines 1-8). Gormley teaches nucleic acid amplification methods such as Tagged PCR which uses a population of two-domain primers such as, for example, in Grothues et al. Nucleic Acids Res. 21(5):1321-2 (1993), incorporated herein by reference in its entirety (interpreted as a primer mixture comprising a primer that binds and DNA- or RNA-specific barcode, claim 5) (paragraph [0082], lines 3-7).
Gormley meets all the limitations of the claims and, therefore, anticipates the claimed invention.
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 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 may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Gormley et al. (hereinafter “Gormley”) (US Patent Application Publication No. 20140194324, published July 10, 2014) in view of Reuter et. al. (hereinafter “Reuter”) (US patent Application Publication No. 20180080021, published March 22, 2018).
The teachings of Gormley as applied to claims 1 and 5 are described supra.
Gormley does not specifically exemplify additional primer mixes (claim 5, in part).
Regarding claim 5 (in part), Reuter teaches methods, compositions, and kits for simultaneously generating RNA and DNA sequencing libraries are disclosed including methods that allow high-throughput amplification and sequencing of both RNA and DNA from a single sample source without the need to divide the sample to separate nucleic acids from each other, wherein all of the preparation steps from harvesting nucleic acids from cells or tissue to preparing RNA and DNA sequencing libraries can be performed with the RNA and DNA pooled together, such that this technology streamlines generation of DNA and RNA sequencing data in combination and makes possible comprehensive genomic and transcriptomic profiling of a cell population concurrently (interpreted as a sample comprising RNA and DNA, claim 1) (Abstract). Reuter teaches that index or barcode sequences can be added to amplicon products to identify whether an amplicon was derived from DNA or RNA and the sample source from which each amplified nucleic acid originated, wherein index/barcode sequences can be used to distinguish amplicons derived from genomic DNA from amplicons derived from RNA (i.e., cDNA) to allow pooling of DNA and RNA from the same sample for high-throughput amplification and sequencing, such as a "DNA index sequence" can be used to identify DNA sequences and an "RNA index sequence" can be used to identify RNA sequences (interpreted as DNA-specific barcodes or RNA-specific barcodes, claim 5) (paragraph [0086], lines 1-11). Reuter teaches that an index/barcode sequence can be added during amplification by carrying out PCR with a primer that contains a region comprising the index/barcode sequence and a region that is complementary to an oligonucleotide adapter sequence (e.g., RNA-specific adapter attached to RNA fragment by ligation or DNA-specific adapter attached to DNA fragment by tagmentation) already ligated to the nucleic acid such that the index/barcode sequence is incorporated into the final amplified nucleic acid product, wherein index/barcode sequences can be added at one or both ends of an amplicon (interpreted as DNA-specific barcodes or RNA-specific barcodes comprising a primer binding sequence, claim 5) (paragraph [0086], lines 23-33). Reuter teaches that oligonucleotides, particularly primer or probe oligonucleotides for amplification or sequencing, can be coupled to labels for detection, such that there are several means known for derivatizing oligonucleotides with reactive functionalities which permit the addition of a label (paragraph [0087], lines 1-5). Reuter teaches quantifying the presence of both DNA-seq and RNA-seq libraries in the pool using droplet digital PCR (ddPCR) (interpreted as amplifying tagged fragments, claim 5) (paragraph [0112], lines 4-6). Reuter teaches that DNA libraries were amplified using standard Nextera indexing primers (interpreted as a primer mix, claim 5) (paragraph[0138], lines 45-46). Reuter teaches PCR reaction to enrich cDNA using custom multiplex primers (interpreted as a primer mix, claim 5) (paragraph [0254]).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of comprehensive genomic and transcriptomic profiling exemplified by Reuters, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of using immobilized transposase and a transposon end for generating an immobilized library of tagged double-stranded target fragments as disclosed by Gormley, to include methods for high-throughput amplification and sequencing as taught by Reuter with a reasonable expectation of success in simultaneously generating RNA and DNA sequencing libraries from the same sample; in generating 5’- and 3’-tagged fragments for massively parallel sequencing; and/or in using index/barcode sequences to quantify the presence of both DNA-seq and RNA-seq libraries in a mixture of nucleic acids.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103(a) as obvious over the art.
Conclusion
Claims 1 and 5 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/Primary Examiner, Art Unit 1684
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