Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Pursuant to a preliminary amendment filed August 9, 2024, claims 2-21 are currently pending.
Therefore, claims 2-21 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed May 23, 2024 is a CON of US Patent Application 18462936, filed September 7, 2023 (now abandoned); which is a CON of US Patent Application 18170285, filed February 16, 2020 (now US11795498); which is a CON of US Patent Application 18047092, filed October 17, 2022 (now US11788122); which is a CON of US Patent Application 17704830, filed March 25, 2022 (now US11479809); which is a CON of US Patent Application 17474922, filed September 14, 2021 (now US11352659); which is a CON of US Patent Application 16013654, filed June 20, 2018 (now abandoned); which is a CON of US Patent Application No. 14111482, filed October 11, 2013 (now US10030261), which is a 35 U.S.C. 371 national stage filing of International Application PCT/EP2012/056823, filed on April 13, 2012, which claims the benefit of United Kingdom Patent Application GB1106254.4, filed on April 13, 2011.
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, United Kingdom Application 1106254.4, filed April 13, 2011, 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 2 does not have support for; “fluorescently labeled frame probes”. Therefore, the priority date for the presently claimed invention is April 13, 2012, the filing date of International Application WO2012140224, filed April 13, 2012.
Applicants are invited to specifically indicate the location of the cited phrase pertinent to claim 2 of the instant application.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on August 20, 2024; November 14, 2024; March 4, 2025 and June 25, 2025 have been considered. Initialed copies of the IDSs accompany this Office Action.
Claim Objections/Rejections
Claim Objection
Claims 5, 8 and 9 are objected to because of the following informalities: Claims 5, 8 and 9 recite the terms "mRNA” and “poly(T)”, where an abbreviation should be spelled out in the first encounter of the claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 112, 2nd paragraph
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 2-21 are rejected under 35 U.S.C. 112, 2nd paragraph as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 2-21 are indefinite because the claims appear to recite both a product and process in the same claim. The examiner cautions that according to the MPEP 2173.05(p)(II) states that a single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112, second paragraph. PXL Holdings v. Amazon.com, Inc., 430 F.2d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005); Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990). For example, claim 2 is directed to “a system for performing spatial analysis of a nucleic acid in a biological sample” such as recited in claim 2, lines 1-2, where instant claim 2 recites, for example: “the biological sample” in line 3; “a barcoded array contacting the biological sample” in line 4; while claim 2 also recites: “a sequencing instrument that identifies a sequence of the nucleic acid from the biological sample” in lines 8-9; and “a computer for performing computational analysis that: (i) registers the biological sample location relative to the barcoded array; and (ii) correlates the sequence of the nucleic acid to the biological sample location” in lines 10-12. Such claims can also be rejected under 35 U.S.C. 101 based on the theory that the claim is directed to neither a “process” nor a “machine,” but rather embraces or overlaps two different statutory classes of invention set forth in 35 U.S.C. 101 which is drafted so as to set forth the statutory classes of invention in the alternative only. Id. at 1551. It is noted that instant claim 2 does not define the product in terms of the process by which it is made (See, MPEP 2173.05(p)); and does not focus on capabilities of the system. Instead, instant claim 2 clearly recites a product, and a process of using the product.
Claim 6 is indefinite for the recitation of the term “wherein the barcoded array comprises…and (ii) a capture domain” such as recited in claim 6, lines 1-3 because claim 6 depends from instant claim 2, wherein claim 2 already recites what the barcoded array comprises, such that a dependent claim cannot now recite that the barcoded array comprises something different (e.g., a barcoded array contacting the biological sample…further comprises one or more fluorescently labeled frame probes) and, thus, the metes and bounds of the claim cannot be determined. The Examiner suggests that Applicant amend the claim to recite, for example, “the barcoded array further comprises.”
Claim 7 is indefinite for the recitation of the term “substantial portion” in claim 7, line 2 because the term “substantial portion” is relative term that renders the claim indefinite. The term “substantial portion” is not defined by the claim, and the Specification does not provide a standard for ascertaining the requisite amount of mRNAs in the biological sample as compared to some other value that qualifies as a “substantial portion”, such that one of ordinary skill in the art would not be reasonably appraised of the scope of the invention and, thus, the metes and bounds of the claim cannot be determined.
Claim 11 is indefinite for the recitation of the term “oriented in the 5’ to 3’ direction” in claim 11, line 2 because the term is unclear with regard to the orientation of the positional domain and the capture domain. It is unclear whether the term refers to the orientation of the positional domain relative to the capture domain (e.g., 5’ positional domain-capture domain-3’), the orientation of the capture domain relative to the positional domain (e.g., 5’-capture domain-positional domain-3’), the orientation relative to a reference point (e.g., a surface) (e.g., surface-5’-capture domain-3’ and/or surface-5’-positional domain-3’), or whether the term refers to something else and, thus, the metes and bounds of the claim cannot be determined.
Claim 14 is indefinite for the recitation of the term “performs next generation sequencing” in claim 14, line 2 because claim 14 depends from instant claim 2, wherein claim 2 does not recite performing sequencing and, thus, the metes and bounds of the claim cannot be determined.
Claim 15 is indefinite for the recitation of the term “computational analysis comprises…with the positional domain” in claim 15, lines 1-2 because claim 15 depends from instant claims 2 and 6, wherein claims 2 and 6 do not recite performing computational analysis. Instead, claim 2 recites that the system comprises a computer that is configured to perform computational analysis, not that computational analysis is performed. No computational analysis is recited in claim 2, such that it cannot comprise a step of correlating gene expression profile of nucleic acids. Moreover, instant claim 2 already recites that the computational analysis comprises registering the biological sample location and correlating the sequence of the nucleic acid, such that claim 15 cannot recite the “computational analysis” comprises something different in the dependent claim and, thus, the metes and bounds of the claim cannot be determined.
Claims 16 and 17 are indefinite for the recitation of the term “wherein the barcoded array comprises at least XXXXX features” such as recited in claim 16, lines 1-2 because claims 16 and 17 ultimately depend from instant claim 2, wherein claim 2 already recites what the barcoded array comprises (e.g., a biological sample, and one or more fluorescently labeled frame probes), such that dependent claims 16 and 17 cannot recite that the barcoded array of claim 2 comprises something different and, thus, the metes and bounds of the claim cannot be determined.
Claim 18 is indefinite for the recitation of the term “stained with hematoxylin or eosin” in claim 18, lines 1-2 because claim 18 depends from instant claim 2, wherein claim 2 does not recite staining the biological sample or a stained biological sample and, thus, the metes and bounds of the claim cannot be determined.
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 § 112, 4th paragraph
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.
Claims 6 and 14-18 are rejected under 35 U.S.C. 112, 4th paragraph 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 6 recites (in part): “wherein the barcoded array comprises a plurality of capture probes…a capture domain” such as recited in claim 6, lines 1-3 because claim 6 depends from instant claim 2, wherein claim 2 already recites what the barcoded array comprises (e.g., a biological sample, and one or more fluorescently labeled frame probes), such that dependent claim 6 cannot recite that the barcoded array of claim 2 comprises something different. Thus, claim 6 is an improper dependent claim 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 14 recites (in part): “wherein the sequencing instrument performs next generation sequencing” such as recited in claim 14, lines 1-2 because claim 14 depends from instant claim 2, wherein claim 2 is directed to a system, such that the system does not perform “next generation sequencing.” Thus, claim 14 is an improper dependent claim 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 15 recites (in part): “wherein the computational analysis comprises correlating a gene expression profile of the nucleic acid with the positional domain” such as recited in claim 15, lines 1-2 because claim 15 depends from instant claims 2 and 6, wherein claims 2 and 6 are directed to a system, wherein the system does not recite performing computational analysis. Instead, claim 2 recites a computer that is configured to perform computational analysis; however, no computational analysis is performed. Moreover, instant claim 2 already recites that the computational analysis comprises registering the biological sample location and correlating the sequence of the nucleic acid, such that claim 15 cannot recite the “computational analysis” comprises something different in the dependent claim
Thus, claim 15 is an improper dependent claim 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.
Claims 16 and 17 recite (in part): “wherein the barcoded array comprises at least 50,000 features” such as recited in claims 16 and 17, lines 1-2 because claims 16 and 17 ultimately depend from instant claim 2, wherein claim 2 already recites what the barcoded array comprises (e.g., a biological sample, and one or more fluorescently labeled frame probes), such that dependent claims 16 and 17 cannot recite that the barcoded array of claim 2 comprises something different. Thus, claims 16 and 17 are improper dependent claims 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 18 recites (in part): “wherein the biological sample is stained with hematoxylin or eosin” such as recited in claim 18, line 1 because claim 18 depends from instant claim 2, wherein claim 2 is directed to a system, wherein the system does not recite performing a step of staining the biological sample. Thus, claim 18 is an improper dependent claim 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.
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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
Claims 2-4, 6, 7, 11-17 and 19-21 are rejected under 35 U.S.C. 102(a) as being anticipated by Chee et al. (hereinafter “Chee”) (US Patent Application Publication No. 20110245111, published October 6, 2011; filed April 5, 2011, effective filing date April 5, 2010) as evidenced by Tifford et al. (hereinafter “Tifford”) (The Journal of Histotechnology, 2009, 32(1), 1-11).
Regarding claim 2, Chee teaches assays and assay systems for use in spatially encoded biological assays comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature (Abstract). Chee teaches an assay system to determine spatial patterns of abundance or activity or both of multiple biological targets at multiple sites in a sample, where the assay system performs the following steps: providing a sample affixed to a support; delivering encoded probes for the multiple biological targets to the multiple sites in the sample in a known spatial pattern, where each encoded probe comprises a probe region that can interact with the biological targets and a coding tag that identifies a location of the site to which the encoded probe was delivered; allowing the encoded probes to interact with the biological targets; separating encoded probes that interact with the biological targets from encoded probes that do not interact with the biological targets; determining all or a portion of a sequence of the encoded probes, and associating the abundance or activity or both of the multiple biological targets to the locations of the sites in the sample, wherein the coding tags comprise oligonucleotides (interpreted as a biological sample; coding tags as a barcoded array contacting the sample; and a coding tag as a barcoded positional domain, claims 2 and 6) (paragraphs [0008]) and [0009]). Chee teaches that the assay system is used to analyze nucleic acids such as by genotyping, quantitation of DNA copy number or RNA transcripts, localization of particular transcripts within samples, and the like (paragraph [0054], lines 1-4). Chee teaches that Figure 4 illustrates a general mechanism for combinatorial encoding scheme of the assay systems of the invention, where nucleic acids in a representative tissue section (shown at 416) are assayed, wherein Figure 4 at A shows two target-specific/encoding oligonucleotide constructs 420 and 422 (e.g., formed between steps 302 and 304 of Figure 3) specifically bound to a target nucleic acid 402 of interest, such that the first encoded probe 420 comprises coding tag 408, associated with, e.g., a universal priming site for amplification of the assay products or an adapter to enable identification of the coding identifiers using sequencing technologies 404 (interpreted as the biological sample contacting the barcoded array; and nucleic acids, claim 2) (paragraph [0062]; and Figure 4). Chee teaches reagent delivery systems of the assay systems comprise an optional imaging means, reagent delivery hardware and control software, wherein reagent delivery can be achieved in a number of different ways, such that delivery can be to many different biological samples at one time, wherein a single tissue section has been exemplified herein; however, multiple biological samples can be affixed and analyzed simultaneously, such as serial sections of a tissue sample can be analyzed in parallel and the data combined to build a 3D map (interpreted as an imager; and tissue sections; and interpreting software and hardware as comprising a computer, claims 2 and 19) (paragraph [0071]). Chee teaches that the delivery system can comprise a microcircuit arrangement including an imager, Such as a CCD or IGFET-based (e.g., CMOS-based) imager and an ultrasonic sprayer for reagent delivery such as described in US Pub. No. 20090197326, which is incorporated herein by reference (interpreted as an imager, also comprising a computer, claim 2) (paragraph [0080], lines 8-13). Chee teaches a high throughput multiplexed assay system that can measure simultaneously the amount and spatial location of a biological target in a biological sample including combining the ability to estimate the relative abundance of different RNA transcripts with the ability to reconstruct an image of spatial patterns of abundance across many locations, which can be as small as or even smaller than individual cells, in a tissue enables many different areas of basic research (interpreted as RNA, claim 4) (paragraph [0088]). Chee teaches that once the in-situ part of the assay is complete, the reaction products are eluted and analyzed by qPCR to determine presence or absence of a product and estimate yield, and by conventional sequencing to determine the structure of the assay products (interpreted as a sequencing instrument, claim 2) (paragraph [0096], lines 1-5). Chee teaches that a 1x3 inch microarray is sufficiently large to permit multiple replicates, wherein this larger set of 24 sequences will require deconvolution, and this is accomplished using high throughput techniques such as next-generation sequencing technologies such as SOLiD technology or Genome Analyzer (interpreted as a sequencing instrument; and comprising a computer, claim 2) (paragraph [0101], lines 6-13). Chee teaches that the invention provides the ability to look at many biological targets in many locations, providing the resolution of in-situ hybridization with the highly-parallel data analysis of sequencing (interpreted as comprising a computer for computational analysis, claim 2) (paragraph [0007], lines 9-11). Chee teaches algorithms and software tools that are specifically designed for analysis of the spatially-associated data generated by the assay systems, including pattern-analysis software and visualization tools, enhance the value of the data generated by the assay systems (interpreting algorithms and software tools and visualization tools as comprising a computer, claim 2) (paragraph [0084], lines 11-15). Chee teaches that the assay system also aid computational efforts to model interacting networks of gene expression in the field of systems biology (interpreted as comprising a computer for computational analysis, claim 2) (paragraph [0089], lines 16-18). Chee teaches that the sample regions of the biological sample can be identified using image processing (e.g., images of cell types differentiated by immunohistochemistry or other staining chemistries) integrated with other features of the assay system, wherein software is used to automatically translate image information into a reagent delivery pattern; and a mechanism to register and align very precisely the biological sample for reagent delivery is thus an important component of the assay systems of the invention, wherein mechanisms include the use of fiducial markers on slides and/or other very accurate physical positioning systems can be adapted to this purpose (interpreting fiducial markers as frame probes, claim 2) (paragraph [0083]). Chee teaches that coding tags are oligonucleotides, mass tags, fluorescent labels, or other moieties (interpreted as fluorescently-labeled frame probes, claim 2) (paragraph [0042], lines 14-17).
Regarding claims 3 and 4, Chee teaches that genomic DNA is assayed as proof of concept for assaying RNA, as it provides a way to establish a single-copy reference signal (interpreting the nucleic acids to be DNA or RNA, claims 3 and 4) (paragraph [0102], lines 1-3).
Regarding claims 6 and 11, Chee teaches that the encoded probes interact with the biological targets being captured by an affinity capture agent (interpreted as comprising a positional domain and a capture domain that are oriented 5’ to 3’, claims 6 and 11) (paragraph [0013]).
Regarding claim 7 (in part), Chee teaches multiple biological targets being assayed and the multiple sites in the sample is greater than 75, 100, 150, 500, 750, 1,000, 5,000, 10,000, 25,000, 50,000, 100,000, 500,000, or 1,000,000 or more including a sequence of at least one hundred thousand encoding probes are determined in parallel (interpreted as positional domain comprises <70% sequence identity across a substantial portion of the mRNAs, claim 7) (paragraph [0011], lines 6-12).
Regarding claim 9 (in part), Chee teaches that the term “oligonucleotide” or “oligo” refers to at least two nucleotides covalently linked together (interpreted as encompassing at least 10 thymidine nucleotides, claim 9) (paragraph [0029], lines 1-3).
Regarding claim 12, Chee teaches that in cases where probes have been transformed via cleavage, the transformed probes can be separated, e.g., by capturing the non-transformed probes via a tag that is removed from the transformed probes during the transformation (e.g., by cleavage), or by adding a new tag at the site of cleavage (interpreted as probes comprising a cleavage domain, claim 12) (paragraph [0045], lines 20-24).
Regarding claim 13, Chee teaches that the ligation and primer regions of the encoding oligonucleotides and probes are universal (interpreted as probes comprising a universal domain, claim 13) (paragraph [0055], lines 12-13). Chee teaches that the first encoded probe 420 comprises coding tag 408, associated with, e.g., a universal priming site for amplification of the assay products or an adapter to enable identification of the coding identifiers using sequencing technologies (interpreted as probes comprising a universal domain, claim 13) (paragraph [0062], lines 8-12).
Regarding claim 14, Chee teaches DNA templates are prepared for sequencing not one at a time, but in a bulk process, and where many sequences are read out in parallel, or alternatively using an ultra-high throughput serial process that itself may be parallelized, wherein such methods include but are not limited to pyrosequencing by 454 Life Sciences; sequencing by ligation in the SOLiD technology; sequencing-by-synthesis using modified nucleotides such as commercialized in TruSeq and HiSeq technology by Illumina; HeliScope and Pac Bio; sequencing-by-ion detection technologies such as in Ion Torrent; sequencing of DNA nanoballs; nanopore-based sequencing technologies; and like highly parallelized sequencing methods (interpreted as performing next generation sequencing, claim 14) (paragraph [0033]).
Regarding claim 15, Chee teaches that there is no practical method exists to analyze at high resolution the spatial expression patterns of large numbers of genes, proteins, or other biologically active molecules simultaneously, such that there is thus a need for reproducible, high-resolution spatial maps of biological molecules in tissues; and the present invention addresses this need (interpreted as correlating gene expression of the nucleic acid with the positional domain (coding tag), claim 15) (paragraph [0005]). Chee teaches assay systems that provide high-resolution spatial maps of biological activity in tissues, wherein the assay system comprises an assay capable of high levels of multiplexing where encoded probes are provided to a biological sample in defined spatial pattern (interpreted as correlating gene expression of the nucleic acid with the positional domain (coding tag), claim 15) (paragraph [0007]).
Regarding claims 16 and 17, Chee teaches multiple biological targets being assayed and the multiple sites in the sample is greater than 75, 100, 150, 500, 750, 1,000, 5,000, 10,000, 25,000, 50,000, 100,000, 500,000, or 1,000,000 or more including a sequence of at least one hundred thousand encoding probes are determined in parallel (interpreting the array to comprise at least 50K or 100K features, claims 16 and 17) (paragraph [0011], lines 6-12).
Regarding claim 18 (in part), Chee teaches an informative image of the biological sample to be assayed can be used to assist in the reagent delivery methods and associated encoding scheme, wherein sample regions of the biological sample can be identified using image processing (e.g., images of cell types differentiated by immunohistochemistry or other staining chemistries) integrated with other features of the assay system (interpreted as staining, claim 18) (paragraph [0083], lines 1-6), where it is known in the art that hematoxylin and eosin are common laboratory stains used to diagnose histopathological conditions as evidenced by Tifford (pg. 10, col 2, last partial paragraph; and pg. 11, col 1, first partial paragraph).
Regarding claim 19, Chee teaches that the 3-dimensional patterns of gene expression are determined by analyzing a series of tissue sections, in a manner analogous to image reconstruction in CT scanning (interpreting the sample to be a tissue section, claim 19) (paragraph [0089], lines 1-4).
Regarding claims 20 and 21, Chee teaches that the samples of the invention include virtually any biological sample or samples that can be affixed to a solid support, wherein exemplary biological samples include tissue sections (e.g., including whole animal sectioning and tissue biopsies), cell populations on slides or culture dishes, and the like, wherein the assay systems are compatible with numerous biological sample types, including fresh samples, such as primary tissue sections, and preserved samples including but not limited to frozen samples and paraformalin-fixed, paraffin-embedded (FFPE) samples (interpreted as fresh frozen tissue sections and FFPE tissue sections, claims 19-21) (paragraph [0052]).
Chee does not specifically exemplify mRNA (claim 5); a capture domain comprising a poly(T) sequence (claims 8 and 9); a capture domain comprising a random or degenerate nucleic acid sequence (claim 10); and a biological sample stained with hematoxylin or eosin (claim 11).
Chee 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(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 2-21 are rejected under 35 U.S.C. 103(a) as being unpatentable over Chee et al. (hereinafter “Chee”) (US Patent Application Publication No. 20110245111, published October 6, 2011; effective filing date April 5, 2010) in view of Chee et al. (hereinafter “Chee ‘979) (International Application WO03002979, published January 9, 2003) as evidenced by Tifford et al. (hereinafter “Tifford”) (The Journal of Histotechnology, 2009, 32(1), 1-11); and Richard Conrad (hereinafter “Conrad”) (US Patent No. 6812341, issued November 2, 2004); and Bong et al. (hereinafter “Bong”) (Molecules and Cells, 2024, 47(12), 1-5).
The teachings of Chee as applied to claims 2-4, 6, 7, 11-17 and 19-21 are described supra.
Chee does not specifically exemplify mRNA (claim 5); a capture domain comprising a poly(T) sequence (claims 8 and 9); a capture domain comprising a random or degenerate nucleic acid sequence (claim 10); and a biological sample stained with hematoxylin or eosin (claim 11).
Regarding claim 5, Chee et al. teach compositions and methods for multiplex decoding of microspheres array sensors (Abstract). Chee et al. teach that Figure 13 depicts construction of probes on bead containing encoding sequences, zipcodes, and a gene-specific sequence, wherein two different encoding cassettes are employed to facilitate the primer extension using primers with universal or degenerate bases; and that Figure 14 depicts incorporation of a cleavable linker between the encoding sequences and gene-specific sequences (pg. 7, first and second full paragraphs; and Figures 13 and 14). Figure 13 is shown below:
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Figure 13
Chee et al. teach forming a surface comprising individual sites on a substrate and distributing microspheres on the surface such that the individual sites comprise microspheres (interpreted as a plurality of features), wherein the microspheres comprise at lease a first and a second subpopulation each comprising a bioactive agent and an identifier binding ligand that will bind a decoder binding ligand such that the identification of the bioactive agent can be elucidated (pg. 4, last full paragraph). Chee ‘979 teaches that the term “target sequence" or grammatical equivalents herein means a nucleic acid sequence on a single strand of nucleic acid, wherein the target sequence can be a portion of a gene, a regulatory sequence, genomic DNA, cDNA, RNA including mRNA and rRNA, or others (interpreting the nucleic acid to include mRNA, claim 5) (pg. 18, first full paragraph, lines 1-3).
Regarding claims 8 and 9 (in part), Chee ‘979 teaches affinity capture utilizing hybridization to attach cloned nucleic acids to beads, wherein polyA + RNA is routinely captured by hybridization to oligo-dT beads, including oligo-dT capture (interpreted as the capture domain comprises a poly(T) sequence comprising at least 10 thymidine nucleotides, claim 8 and 9) (pg. 17, first full paragraph), wherein it is known that a poly(dT) nucleic acid comprises at least 10 contiguous T residues; wherein “oligo-dT” is used as a targeting agent for poly(A) RNA, and refers to a synthesized DNA oligonucleotide of which > 90% is the nucleobase T as evidenced by Conrad (col 12, lines 28-33); and that the general length of oligo-dT primers is 12-18 nucleotides for binding to the poly(A) tail of most mRNAs without specific binding as evidenced by Bong (pg. 2, col 1, last full paragraph).
Regarding claim 10, Chee ‘979 teaches that bioactive agents can be obtained from a variety of sources including libraries of synthetic or natural compound, such that bioactive agents are random peptides from about 5 to about 30 amino acids (corresponding to random nucleic acid sequence, claim 10) (pg. 13, last partial paragraph, lines 1-2; and pg. 14, third full paragraph, lines 1-4). Chee ‘979 teaches that a degenerate probe sequence is attached to one or more constant probe regions, wherein “constant” probe region is meant a portion of the probe that is invariant among a population of decoder probes, such that the degenerate region or variable region is flanked by constant regions (corresponding to a capture probe comprising degenerate nucleic acid sequence, claim 10) (pg. 36, last partial paragraph; and pg. 37, first partial paragraph).
Regarding claim 18, Chee ‘979 teaches labeling binding ligand-DBL pairs, wherein suitable labels include eosin (interpreted as eosin, claim 18) (pg. 28, third full paragraph, lines 11-14). Chee ‘979 teaches discriminant analysis and cluster algorithms and computer apparatus are used to analyze the decoding data from the arrays of the invention, including an optical imaging system (pg. 46, third full paragraph).
Although the combined references of Chee and Chee ‘979 do not specifically exemplify staining a biological sample with hematoxylin or eosin, Chee does teach that an informative image of the biological sample to be assayed can be used to assist in the reagent delivery methods and associated encoding scheme, wherein sample regions of the biological sample can be identified using image processing (e.g., images of cell types differentiated by immunohistochemistry or other staining chemistries) integrated with other features of the assay system (interpreted as staining, claim 18) (paragraph [0083], lines 1-6), where it is known in the art that hematoxylin and eosin are common laboratory stains used to diagnose histopathological conditions as evidenced by Tifford, while Chee ‘979 teaches labeling binding ligand-DBL pairs, wherein suitable labels include eosin, and an optical imaging system, such that one of ordinary skill in the art would clearly recognize that staining techniques including immunohistological staining of cells and tissues include staining with hematoxylin or eosin.
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Moreover, “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 analyzing gene expression profiling including for RNA expression profiling as exemplified by Chee ‘979, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the assay system comprising encoding oligonucleotide primers coupled to probes, and biological samples including tissue sections immobilized on a substrate surface as exemplified by Chee to include probes comprising encoding sequences, zipcodes, a gene-specific sequence, and degenerate sequences including probes attached to beads as disclosed by Chee ‘979 with a reasonable expectation of success in creating a multiplex assay system and optical imaging system for the simultaneous measurement of gene expression and/or quantitation of the amount of individual mRNA at specific spatial locations in a biological sample including a tissue sample; and/or for the multiplexed detection and identification of different transcripts within a biological sample, wherein assay results are mapped back to specific locations in the biological sample to reveal different spatial patterns of gene expression, which can be indicative of a specific disease or a specific disease pathology.
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 as obvious over 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 2-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claim 1 of copending Application No. 19/022,051.
US Patent Application 19/022,051 recites: A system for performing spatial analysis of a nucleic acid in a biological sample, wherein the system comprises: (a) the biological sample; (b) a barcoded array contacting the biological sample, wherein the barcoded array further comprises one or more fluorescently labeled frame probes; (c) an imager configured to obtain an image of the biological sample and the one or more fluorescently labeled frame probes; (d) a sequencing instrument that identifies a sequence of the nucleic acid from the biological sample; and (e) a computer for performing computational analysis that: (i) registers the biological sample location relative to the barcoded array; and (ii) correlates the sequence of the nucleic acid to the biological sample location (claim 1).
Claim 1 of copending Application 19/022,146.
US Patent Application 19/022,146 recites: A system for performing spatial analysis of a nucleic acid in a biological sample, wherein the system comprises: (a) the biological sample; (b) a barcoded array contacting the biological sample, wherein the barcoded array further comprises one or more fluorescently labeled frame probes; (c) an imager configured to obtain an image of the biological sample and the one or more fluorescently labeled frame probes; (d) a sequencing instrument that identifies a sequence of the nucleic acid from the biological sample; and (e) a computer for performing computational analysis that: (i) registers the biological sample location relative to the barcoded array; and (ii) correlates the sequence of the nucleic acid to the biological sample location (claim 1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant Application and the claims of 19/022,051 and 19/022,146 are directed to a system for performing spatial analysis of a nucleic acid in a biological sample, the system comprising a biological sample, a barcoded array, an imager, a sequencing instrument and a computer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 2-21 are rejected.
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/AMY M BUNKER/
Primary Examiner, Art Unit 1684
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