CTNF 18/690,840 CTNF 77002 DETAILED CORRESPONDENCE Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. This action is in response to the papers filed August 26, 2024. Currently, claims 1, 3-11, 13-21, 24 are pending. Priority This application claims priority to PNG media_image1.png 72 646 media_image1.png Greyscale Drawings The drawings are acceptable. Claim Rejections - 35 USC § 112- Second 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. 07-34-01 AIA Claim s 1, 3-11, 13-21, 24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. 07-34-03 AIA The term “ substantially ” in claim 1 is a relative term which renders the claim indefinite. The term “ substantially ” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claims depending on Claim 1 and Claim 24 are similarly indefinite . Claim 6 requires the last measurement is linked to the first measurement but it is unclear what “linked” requires. If the recitation “linked” only means they are from the same tissue sample, Claim 1 already requires this limitations. Thus, it is unclear what linked means. The metes and bounds of the claimed invention are unclear. Claim 13 is directed to the biopsy comprises a sample from a tumor, tissue ….and microbial community. It is unclear what type of sample has all of these elements since CNS tissue, developing tissue and lymphatic tissue are such diverse samples. Applicant may have intended this to be a list of alternatives rather than requiring all of the sample types. Clarification is required. Claim 13 lacks proper antecedent basis. Claim 13 requires “the biopsy” comprises a sample from a tumor, tissue…. Claim 13 depends on Claim 11 and Claim 1. The prior claims do not recite a biopsy. Thus, “the biopsy” lacks proper antecedent basis . Claim Rejections - 35 USC § 112- 07-36 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. 07-36-01 AIA Claim s 4-5 are rejected under 35 U.S.C. 112(d) or pre-AIA 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 4 requires using the same or different techniques. This limitation does not appear to limit Claim 1 in any way since Claim 1 also may include with the same or different techniques. The claims are identical in scope. Claim 5 similarly fails to limit Claim 3 because Claim 5 requires the one or more additional measurements may be carried out in any order. Claim 3 did not require they had a particular order, thus, it is unclear how requiring they may be in any order limits the scope of the claim . Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-06 AIA 15-10-15 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. 07-15-aia AIA Claim(s) 1, 3-10, 13-21 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Wang et al. (Biotechnology Journal, Vol. 16, NO. 2100041, May 28, 2021) . Wang teaches spatial transcriptomics and proteomics technologies for deconvoluting a tumor microenvironment. Wang teaches spatially-resolving high-plex molecular profiling technologies (abstract). Wang teaches HDST, high definition spatial transcriptomics that employs spatial barcoding techniques (page 2, col. 2). As seen in Figure 1, HDST illustrates tissue was cryosected and RNA was related and captured via polyA tails in -situ, followed by reverse transcription and sequencing. This sequencing and mapping is additional measurement of different sequences (limitations of Claim 3-5). The tissue was measured for H&E staining and amplification/sequencing and mapping. The H&E staining does not substantially disrupt the integrity of the tissue sample. Wang also demonstrates Visium ST performs a series of steps and measurements (see Figure 1). PNG media_image2.png 242 1252 media_image2.png Greyscale With respect Claim 6, all of the measurements are linked to the same tissue. With respect to Claim 7, Wang teaches HDST and Visium ST each rely upon sectioning the tissue before labeling with barcodes. With respect to Claim 8, Wang teaches cryosectioning (page 2, col. 2). With respect to Claim 9-10, Wang illustrates the nucleic acids of HDST and Visium ST each have barcodes. With respect to Claim 13, Wang teaches the tissue samples are tumor samples. With respect to Claim 14-19, Wang further teaches Imaging MS is step of imaging scan followed by IMS. Claims 15-19 are directed to limiting alternative elements of Claim 14. With respect to Claims 20-21, each of HDST, Visium ST teach analysis of RNA, a nucleic acid in tissue . 07-15-aia AIA Claim(s) 1, 3-7, 9-11, 13-21 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Villacampa et al. (bioRxiv preprint doi: https://doi.org/10.1101/2020.07.24.219758, July 25, 2020) . Villacampa teaches genome-wide spatial expression profiling in FFPE tissues. Villacampa teaches tissue sections were placed on Visium Spatial gene expression slides and staining was peformed (Page 13). Slides were scanned under high- resolution microscope to obtain tissue tile images and software to stitch the high-resolution images together (page 13-14). Villacampa teaches the Visium slides were incubated, cells were lysed and mRNA was obtained, captured and sequence was determined (page 14-18). Thus, the method has at least 2 measurements as well as additional measurements (limitations of Claims 3-5). With respect Claim 6, all of the measurements are linked to the same tissue. With respect to Claim 11, Villacampa teaches the gynecological carcinosarcoma sections were 12um thick and the mouse brain was 10 um thick (page 13). With respect to Claim 13, Villacampa teaches performing genome-wide spatial analysis of mRNA in FFPE tissue section from mouse brain, gynecological carcinosarcoma. With respect to Claim 14-19, Villacampa further teaches performing HE imaging under a high-resolution microscope. Claims 15-19 are directed to limiting alternative elements of Claim 14. With respect to Claims 20-21, the Visium slides were incubated, cells were lysed and mRNA was obtained, captured and sequence was determined for nucleic acids (page 15-17) . Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-20-02-aia AIA This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. 07-21-aia AIA Claim 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Villacampa et al. (bioRxiv preprint doi: https://doi.org/10.1101/2020.07.24.219758, July 25, 2020) in view of Neumann et al. (J. of Am. Society for Mass Spectrometry, Vol. 31, pages 2401-2415, 2020) . Villacampa teaches genome-wide spatial expression profiling in FFPE tissues. Villacampa teaches tissue sections were placed on Visium Spatial gene expression slides and staining was peformed (Page 13). Slides were scanned under high-resolution microscope to obtain tissue tile images and software to stitch the high-resolution images together (page 13-14). Villacampa teaches the Visium slides were incubated, cells were lysed and mRNA was obtained, captured and sequence was determined (page 14-18). Villacampa teaches the gynecological carcinosarcoma sections were 12um thick and the mouse brain was 10 um thick (page 13). Villacampa teaches performing genome-wide spatial analysis of mRNA in FFPE tissue section from mouse brain, gynecological carcinosarcoma. Villacampa does not teach obtaining a mass spec measurement using MALDI-MS. However, Neumann teaches multimodal imaging mass spectrometry as the next generation molecular mapping in biology and medicine. Neumann teaches mass spec can be complemented by the addition of other orthogonal, chemically informative imaging technologies to maximize the information gained from a single experiment and enable deeper understanding of biological processes. Neumann teaches MALDI may be integrated with other analytical modalities such as microscopy, transcriptomics, spectroscopy and electrochemistry in field termed multimodal imaging. Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention to have modified the method for genome wide spatial expression profiling of Villacampa to add additional analytical modalities such as MALDI, as taught by Newmann to maximize information from a single experiment. Newmann teaches coupling IMS with transcriptomics would enable simultaneous correlation of gene expression to gene products and biproducts (page 2407, col. 1). Conclusion No claims allowable over the art. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached on (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682 May 4, 2026 Application/Control Number: 18/690,840 Page 2 Art Unit: 1682 Application/Control Number: 18/690,840 Page 3 Art Unit: 1682 Application/Control Number: 18/690,840 Page 4 Art Unit: 1682 Application/Control Number: 18/690,840 Page 5 Art Unit: 1682 Application/Control Number: 18/690,840 Page 6 Art Unit: 1682 Application/Control Number: 18/690,840 Page 7 Art Unit: 1682 Application/Control Number: 18/690,840 Page 8 Art Unit: 1682 Application/Control Number: 18/690,840 Page 9 Art Unit: 1682
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