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 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.
Claim(s) 1,2, 6-10, 13, and 15-20 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Chee et al. (US20190300945A1, disclosed in the IDS).
Regarding claim 1, Chee discloses a method of detecting an nucleic acid in a biological sample, the method comprising: (a) hybridizing a first probe oligonucleotide and a second probe oligonucleotide to an nucleic acid in a biological sample on a first substrate, wherein the first probe oligonucleotide and the second probe oligonucleotide each comprise a sequence that is substantially complementary to a first sequence and a second sequence of the nucleic acid, respectively, and wherein the second probe oligonucleotide comprises an capture probe binding domain; (e.g. two target-specific/encoding oligonucleotide constructs specifically bound to a target nucleic acid of interest in a sample [Fig. 4A])
(b) coupling the first probe oligonucleotide and the second probe oligonucleotide, thereby generating an connected probe; (e.g. Step 302 of Fig 3 shows one of the oligonucleotide probes is extended to incorporate the nucleic acid sequence and ligated to the other probe to form an extended probe [paragraph 0054]).
(c) aligning the first substrate with a second substrate comprising an array, such that at least a portion of the biological sample is aligned with at least a portion of the array, wherein the array comprises a plurality of capture probes, wherein a capture probe of the plurality of capture probes comprises: (i) a spatial barcode and (ii) a capture domain; (e.g. In Fig. 1, Step 120 involves delivering encoded probes to the biological sample in a predetermined spatial arrangement. Encoded probes comprise probes, which can interact “with biological targets of interest, and coding tags, which identify the positions in the sample of the biological targets being assayed [paragraph 0042])
(d) releasing the connected probe from the nucleic acid when the biological sample is aligned with at least a portion of the array (e.g. “the encoded probes are eluted” [paragraph 0056])
(e) hybridizing the exogenous capture probe binding domain of the exogenous connected probe to the capture domain of the capture probe. (e.g. , encoding oligonucleotides may be ligated to sequencing primers [paragraph 0056] or sequencing adapters [paragraph 0122])
Regarding claim 2, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses the nucleic acid comprises viral DNA or viral RNA [paragraph 0099]. The limitation that nucleic acid is “exogenous” does not impose structural or procedural distinction, and the obviousness reasoning set forth for claim 1 applies equally to the dependent claim 2.
Regarding claim 6, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses analyzing an analyte in the endogenous genome of the biological sample, wherein the biological sample [abstract] is on the first substrate, the method comprising: hybridizing a first probe oligonucleotide and a second probe oligonucleotide to the analyte, wherein the first probe oligonucleotide and the second probe oligonucleotide each comprise a sequence that is substantially complementary to a first sequence and a second sequence of the analyte, respectively, and wherein the second probe oligonucleotide comprises a capture probe binding domain; coupling the first probe oligonucleotide and the second probe oligonucleotide, thereby generating a connected probe prior to aligning the first substrate with the second substrate (e.g. Step 302 of Fig 3 shows one of the oligonucleotide probes is extended to incorporate the nucleic acid sequence and ligated to the other probe to form an extended probe [paragraph 0054]); when the biological sample is aligned with at least a portion of the array, releasing the connected probe from the analyte (e.g. “the encoded probes are eluted” [paragraph 0056]); and hybridizing the connected probe to the second capture domain of a second capture probe on the array, wherein the second capture probe further comprises a second spatial barcode.( e.g. coupling spatial encoding agents with oligonucleotide probes allow for determining and associating the abundance or activity or both of multiple biological targets to the locations of multiple sites in the sample. [paragraph 0014]).
Regarding claim 7, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 6 as discussed fully above and incorporated here. Chee further discloses the analyte comprises DNA or RNA [paragraph 0099].
Regarding claim 8, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 6 as discussed fully above and incorporated here. Chee further discloses determining (i) all or a part of a sequence of the connected probe, or a complement thereof; (ii) the sequence of the second spatial barcode, or a complement thereof, to determine the location and/or abundance of the analyte in the biological sample. (e.g. determining all or a portion of a sequence of the encoded probes using high-throughput sequencing, and associating the abundance or activity or both of multiple biological targets to the locations of multiple sites in the sample. [paragraph 0014])
Regarding claim 9, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 6 as discussed fully above and incorporated here. Chee further discloses the coupling of the first probe oligonucleotide and the second probe oligonucleotide comprises ligating the first probe oligonucleotide and the second probe oligonucleotide. (e.g. Step 302 of Fig 3 shows one of the oligonucleotide probes is extended to incorporate the SNP sequence and ligated to the other probe to form an extended probe [paragraph 0054]).
Regarding claim 10, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses determining location and/or abundance of a protein in the biological sample [paragraph 0009] , the method comprising:
prior to aligning the first substrate with the second substrate, contacting the biological sample with a plurality of analyte capture agents, wherein an analyte capture agent of the plurality of analyte capture agents comprises an analyte binding moiety and a capture agent barcode domain, wherein the analyte binding moiety specifically binds to the protein, and wherein the capture agent barcode domain comprises an analyte binding moiety barcode and a capture handle sequence; (e.g. Protein capture probes are typically conjugated or otherwise linked to oligonucleotide encoding agents. The encoding agents would also include a nucleotide sequence component that allows for identification of the protein probe. [paragraph 0059])
when the biological sample is aligned with at least the portion of the array, hybridizing the capture handle sequence to a third capture domain of a third capture probe on the array, wherein the third capture probe further comprises a third spatial barcode; (e.g. coupling spatial encoding agents with oligonucleotide probes allow for determining and associating the abundance or activity or both of multiple biological targets to the locations of multiple sites in the sample. [paragraph 0014]).
determining (i) all or a part of a sequence of the capture agent barcode domain, or a complement thereof, and (ii) the sequence of the third spatial barcode, or a complement thereof, to determine the location and/or abundance of the protein in the biological sample. (e.g. determining all or a portion of a sequence of the encoded probes using high-throughput sequencing, and associating the abundance or activity or both of multiple biological targets to the locations of multiple sites in the sample. [paragraph 0014])
Regarding claim 13, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses determining (i) all or a part of the sequence of the exogenous connected probe, or a complement thereof, and (ii) the sequence of the spatial barcode, or a complement thereof, and wherein the method further comprises using the determined sequences of (i) and (ii) to determine the location and/or abundance of the exogenous nucleic acid in the biological sample. (e.g. determining all or a portion of a sequence of the encoded probes using high-throughput sequencing, and associating the abundance or activity or both of multiple biological targets to the locations of multiple sites in the sample. [paragraph 0014])
Regarding claim 15, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses the biological sample is a tissue sample. [paragraph 0004]
Regarding claim 16, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses biological sample is a fixed tissue sample [paragraph 0052]
Regarding claim 17, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 16 as discussed fully above and incorporated here. Chee further discloses the fixed tissue sample is a formalin fixed paraffin embedded (FFPE) tissue sample. [paragraph 0052]
Regarding claim 18, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 15 as discussed fully above and incorporated here. Chee further discloses the tissue sample is a fresh frozen tissue sample.[paragraph 0052]
Regarding claim 19, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 15 as discussed fully above and incorporated here. Chee further discloses the tissue sample is fixed and stained prior to step (a). [paragraph 0084]
Regarding claim 20, Chee discloses a method of detecting an exogenous nucleic acid in a biological sample, the method comprising:
(a) hybridizing a first exogenous probe oligonucleotide and a second exogenous probe oligonucleotide to an exogenous nucleic acid in a biological sample on a first substrate, wherein the first exogenous probe oligonucleotide and the second exogenous probe oligonucleotide each comprise a sequence that is substantially complementary to a first sequence and a second sequence of the exogenous nucleic acid, respectively, and wherein the second exogenous probe oligonucleotide comprises an exogenous capture probe binding domain; ; (e.g. two target-specific/encoding oligonucleotide constructs specifically bound to a target nucleic acid of interest in a sample [Fig. 4A])
(b) coupling the first exogenous probe oligonucleotide and the second exogenous probe oligonucleotide, thereby generating an exogenous connected probe; (b) coupling the first exogenous probe oligonucleotide and the second exogenous probe oligonucleotide, thereby generating an exogenous connected probe; (c) aligning the first substrate with a second substrate comprising an array, such that at least a portion of the biological sample is aligned with at least a portion of the array, wherein the array comprises a plurality of capture probes, wherein a capture probe of the plurality of capture probes comprises: (i) a spatial barcode and (ii) a capture domain; (e.g. In Fig. 1, Step 120 involves delivering encoded probes to the biological sample in a predetermined spatial arrangement. Encoded probes comprise probes, which can interact “with biological targets of interest, and coding tags, which identify the positions in the sample of the biological targets being assayed [paragraph 0042])
(d) releasing the capture probe from the array when the biological sample is aligned with at least a portion of the array; (e.g. “the encoded probes are eluted” [paragraph 0056])
(e) hybridizing the exogenous capture probe binding domain of the exogenous connected probe to the capture domain of the capture probe. (e.g. , encoding oligonucleotides may be ligated to sequencing primers [paragraph 0056] or sequencing adapters [paragraph 0122])
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 (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 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.
Chee et al.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chee et al. (US20190300945A1, disclosed in the IDS).
Regarding claim 11, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses the releasing step comprises contacting the biological sample with a reagent medium comprising proteinase (e.g. releasing ligated, encoded probes from a biological sample following interaction with a target, including release by protease-mediated cleavage of probe components in the sample. After cleavage, the probes are separated and eluted from the biological sample [paragraph 0045]. Although Chee does not recite proteinase K or pepsin, the selection of a particular protease from among know proteases suitable for cleavage of probes represents an obvious matter of routine optimization. Proteinase K or pepsin were well known in the art for protein digestion and facilitate release of nucleic acid probes from biological samples. Accordingly, it would have been obvious to one of ordinary skill in the art to use the proteinase K or pepsin if appropriate.)
Chee et al., Frenz et al., and Srivastava
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chee et al. (US20190300945A1, disclosed in the IDS) in view of Frenz et al. (US20200277664A1, disclosed in the IDS) and Srivastava (CGT Insights, 2(5):553-575, 2016).
Regarding claim 3, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. However, Chee does not disclose the analyte sample is an adeno-associated virus (AAV) nucleic acid, wherein the AAV is selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, and AAV9.
Frenz discloses exogenous viral vectors analytes such as AAV nucleic acids may be introduced into biological samples [paragraph 1132].
Srivastava teaches that AAV1-9 are well-characterized, commonly used, and conventional AAV serotypes routinely employed in research and clinical applications, representing predictable variants with the AAV genus [page 553 and 555].
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the spatial nucleic-acid detection method taught by Chee to AAV nucleic acids taught by Frenz, and to select AAV1-9 as the AAV serotypes as the exogenous analytes. Chee discloses a platform level method for detecting nucleic acid in biological sample that is known in the art, while Frenz established AAV nucleic acid as one of potential exogenous viral analytes routinely introduced into and analyzed within biological tissues. Further, as evident by the well-established state of the art, AAV1-AAV9 represent conventional, widely used, and well-characterized AAV serotypes that were employed in therapeutic contexts at the time of the invention, such that selecting any of AAV1-AAV9 would have constituted a predictable choice from finite set of known options within the AAV genus. Accordingly, applying Chee’s workflow to AAV nucleic acids and selecting AAV1-AAV9 as representative serotypes would have been a routine and predictable variation yielding no unexpected results, and therefore would have been obvious to person of ordinary skill in the art.
Chee et al. and Frenz et al
Claim(s) 4, 5, 12, and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chee et al. (US20190300945A1, disclosed in the IDS) in view of Frenz et al. (US20200277664A1, disclosed in the IDS).
Regarding claim 4, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses the nucleic acid comprises DNA or RNA [paragraph 0099]. However, Chee does not disclose the virus integrates into the host genome is selected from a retroviral vector, an arenavirus vector, a herpes virus vector, an Epstein-Barr Virus vector, or an adenovirus vector.
Frenz discloses the spatial analysis methods can be used to detect lentiviral vectors and retroviral vectors. Examples comprising plasmids, transposons, cosmids, and various viral vectors, such as adenoviral vectors (including those designated pSV or pCMV), adeno-associated virus (AAV) vectors, lentivirus vectors, and retroviral vectors [paragraph 1132].
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the spatial viral nucleic-acid detection method taught by Chee to virus nucleic acids taught by Frenz. Chee discloses probe-based hybridization, ligation, spatially capture, and does not limit detection to nucleic acids based on whether they are episomal or integrated to a host gene. Frenz further teaches the use of viral vectors as exogenous nucleic acids introduced into biological samples, including viral nucleic acids that are known to integrate into or persist within host’s genomes. The viral nucleic acids are known in the art as viral vectors capable of genome integration or genome persistence and are routinely analyzed using nucleic acid-based detection methods. Therefore, it would be obvious to a person of ordinary skill in the art to apply the disclosed spatial viral nucleic acids detection method to genome integrated viral nucleic acids from any of the listed viral vectors, representing a predictable selection of known viral species yielding predictable results. This reasoning is consistent with KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B).
Regarding claim 5, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses the method can be used to detect nucleic acids including RNA transcripts [0042]. However, Chee not disclose the RNA is from a reporter gene, wherein the reporter gene is selected from the group consisting of green fluorescent protein (GFP), Cerulean, tdTomato, and mCherry.
Frenz discloses the spatial analysis methods can be used to detect reporter labels such as GFP [paragraph 0179]. The rationale for combining Chee and Frenz with respect to claim 5 is the same as set forth in claim 4 and is incorporated here by reference. As discussed above, Chee teaches spatial detection of RNA transcripts without limitation as to RNA source, and Frenz teaches the use of reporter genes, including GFP and related reporters, as exogenous nucleic acids in biological samples. Therefore, it would have been prima facie obvious to apply Chee’s workflow to RNA derived from reporter genes.
Regarding claim 12, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses methods for performing integrated in situ spatial assays in which a biological sample contacts with multiple substrate(s) comprising a spatial barcoded capture agents [paragraphs 0088 and 0096]. Chee teaches contacting biological sample with the array substrate under appropriate conditions to enable capture of analytes and generation of spatially labelled polynucleotides. Thus, Chee discloses the functional concept of aligning a biological sample on multiple substrates in the presence of a reagents medium to enable spatial analysis. However, Chee does not explicitly disclose the mechanical implementation of the alignment, including mounting the first substrate on a first member of a support device, mounting the second substrate on a second member of the support device, or operating an alignment mechanism of the support device to move the first member and/or the second member relative to one another to achieve alignment and reagent-mediated contact.
Frenz discloses physical support devices and fluidic systems for spatial assays, including flow cells that retain substrates, deliver reagents, and enable controlled contact and alignment between samples and capture probe arrays. In example 2 [paragraph 1363], Frenz teaches that the spatial assay may be performed with manual reagents addition or “with aid of a flow cell to automatically add reagents, sample, or conduct multiple rounds of in-situ sequencing”, and further disclosing washing reagents and probes in and out of the flow cell during operation. In example 3 [paragraph 1364-1365], Frenz similarity describes providing substrate covered by capture probes, contacting the biological sample with the substrates allowing barcoded labeling agents (e.g., an antibody-DNA conjugate) to interact with the capture probes, and performing in-situ sequencing within defined areas of the substrate, again stating the experiment may be performed using a flow cell to automatically add reagents, samples, and conduct sequencing. Taken together, Frenz teaches (i) mounting substrates within a flow cell support device, (ii) applying a reagent medium to the substrates, and (iii) enabling controlled mechanical alignment/contact between biological sample and the probe array through flow cell architecture.
As of the application’ s effective filing date, one of ordinary skill in the art would have had a reasonable expectation of success and motivated to combine these teachings to implement the multi-substrate spatial assay methods of Chee using the flow cell-based support and alignment systems taught by Frenz, because Frenz provides an established mechanical solution for retaining substrates, delivering reagents, and enabling controlled alignment and contact during special assays. Combining Frenz’s flow cell and support device architecture with Chee’s special assay methods is applying a known mean of substrate handling and alignment, yielding predictable results without altering the underlying assay chemistry or spatial analysis workflow. Such a combination represents application of a known hardware to facilitate known spatial technique, and would have been a routine design choice for person of ordinary skill in the art seeking to automate reagent delivery, improve reproducibility, and control substrate alignment during special analysis. This reasoning is consistent with KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, A and C).
Regarding claim 14, Chee discloses a method of detecting a nucleic acid in a biological sample of claim 1 as discussed fully above and incorporated here. Chee further discloses the capture probe may comprises coding tag associate with a universal priming and probe region that may interact with the biological targets [paragraph 0114]. However, Chee does not disclose capture probe is a poly(T) sequence, and wherein the capture probe further comprises one or more functional domains; a unique molecular identifier (UMI), a cleavage domain, and combinations thereof.
Frenz discloses the capture probe comprises a poly(T) sequence [paraph 0044], and wherein the capture probe further comprises one or more functional domains; a unique molecular identifier (UMI) [paragraph 0060], a cleavage domain [paragraph 0016], and combinations thereof.
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the capture probe of Chee to comprise a poly(T) sequence and more additional functional domains, including a UMI and/or a cleavage domain, as taught by Frenz, in order to facilitate efficient capture, sequencing-based detection, and accurate quantification of nucleic acids. Such modification represents predictable use of prior art elements according to their established functions and yields no unexpected results. This reasoning is consistent with KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, C).
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.
U.S. 17/180,325
Claim(s) 1, 2-5, 7-10, 14-16, and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 2, 28, 58, 95, 102-104 of U.S. Application No. 17/180,325 (the ‘325 application). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding present claim 1 and 20, the claims of the ‘325 applicationpatent disclose a method of analyzing a biological sample comprising contacting the biological sample with a pair of nucleic acid probes that hybridized to a target nucleic acid, generating a ligation product from template ligation of the probes, capturing the ligation product using capture agents associated with a second substrate comprising spatial barcodes, and correlate the molecular information with spatial location (e,g, as per claims 2 and 28 of ‘325 application)
Regarding present claim 2-5, 7, the claims of the ‘325 applicationpatent disclose the target nucleic acid is an RNA molecule (e,g, as per claims 2, 102, and 103 of ‘325 application).
Regarding present claim 8-10, the claims of the ‘325 applicationpatent disclose determining spatial ligation and/or abundance of target nucleic acid by correlating molecular sequence information with a spatial barcode captured on the second substrate (e,g, as per claims 2 and 58 of ‘018 patent).
Regarding present claim 14, the claims of the ‘325 applicationpatent disclose the capture probe comprises one or more functional domains, spatial barcode, a cleavage domain, and combinations thereof (e,g, as per claims 95 of ‘325 application).
Regarding present claim 15-16, the claims of the ‘325 applicationpatent disclose biological sample is a tissue sample (e,g, as per claims 104 of ‘325 application patent).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
U.S. 12,188,085 B2
Claim(s) 1, 6-10, 14-16, and 20 rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1, 7,21, 24, 34-37, 64, 71, 84, and 88-93 of U.S. Patent No. 12188085 (the ‘085 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding present claim 1 and 20, the claims of the ‘085 patent disclose a method of analyzing a biological sample comprising contacting the biological sample with spatial probes targeted to analyte molecule, generating product comprising analyte sequence information, spatial location information, and determining the location and/or abundance of the analyte molecule in the biological sample by sequencing the product (e,g, as per claims 1, 88, and 93 of ‘085 patent).
Regarding present claim 6, the claims of the ‘085 patent disclose further analyzing an endogenous analyte in the biological sample using spatial probes targeted to the analyte, generating product comprising analyte sequence information, spatial location information, and determining the location of the analyte within the biological sample (e,g, as per claims 1, 34-37 of ‘085 patent).
Regarding present claim 7-9, the claims of the ‘085 patent disclose analytes may comprise DNA or RNA, that probe coupling may comprise ligation or extension, and that location and/or abundance is determined by sequencing the barcode sequences associate with the probes (e,g, as per claims 36, 37, 64, and 65 of ‘085 patent).
Regarding present claim 14, the claims of the ‘085 patent disclose spatial probes comprising one or more functional domains, barcode sequences correspond to spatial location or migration length, cleavage domain, can combination thereof (e,g, as per claims 1, 24, and 93 of ‘085 patent).
Regarding present claim 15 and 16, the claims of the ‘085 patent disclose the biological sample is a tissue sample, including fixed tissue (e,g, as per claims 84 and 86 of ‘085 patent).
U.S. 17/853,256
Claim(s) 1-5, 7, 14, 15, and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1, 22, 25, 27, 30, 36, 42, 47, 49, 52, and 54 of U.S. Application No. 17/853,256 (the application ‘256). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding present claim 1 and 20, the claims of the application ‘256 disclose a method of analyzing a biological sample comprising contacting the biological sample with labeling agents comprising an analyte binding moiety conjugated to a reporter oligonucleotide, hybridizing a nucleic acid probe comprising a barcode sequence to the reporter oligonucleotide, amplifying the nucleic acid probe, hybridize the probe to target nucleic acid, and detecting the probe at spatial location of the biological sample, thereby and determining the location and/or abundance of the target nucleic acid. (e,g, as per claims 1 and 22 of application ‘256).
Regarding present claim 2-5, 7, the claims of the application ‘256 disclose the target nucleic acid is an RNA or DNA molecule (e,g, as per claims 6, 8, 11, and 15 of application ‘256).
Regarding present claim 14, the claims of the application ‘256 disclose further the capture probe comprises a poly(T) sequence, and wherein the capture probe further comprises one or more functional domains, a unique molecular identifier (UMI), a cleavage domain, and combinations thereof (e,g, as per claims 22 and 27 of application ‘256).
Regarding present claim 15, the claims of the application ‘256 disclose the biological sample is a tissue sample (e,g, as per claims 54 of application ‘256).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Khai Quynh Tien Pham whose telephone number is (571)272-6998. The examiner can normally be reached M-T, 9-4 ET.
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/KHAI QUYNH TIEN PHAM/ Examiner, Art Unit 1684
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684