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 .
Claims 1-2, 4-7, 10, 13-29, 32-33, and 35-37 are pending. Claims 20-29, 32-33, and 35-37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 3, 8-9, 11-12, 30-31, and 34 are cancelled. Claims 1, 7, 10, 13, and 18 are amended. Claims 1-2, 4-7, 10, and 13-19 are currently under examination.
Response to Amendment
The Amendment filed 11/21/25 has been entered. Claims 1-2, 4-7, 10, 13-29, 32-33, and 35-37 are pending. Applicant’s amendments to claims 1, 7, and 18 have overcome the objections and 112(b) rejection previously set forth in the Non-Final Office Action mailed 8/21/25.
Response to Arguments
Applicant's arguments, see pages 9-12, filed 11/21/25, with respect to the rejections of claims 1-2, 4-7, 10, and 13-19 under 35 USC 101 have been fully considered and are found unpersuasive, and the 101 rejections documented in the Non-Final mailed 8/21/25 have been revised to address claim amendments filed 11/21/25 in this Final Office Action. More detailed responses to Applicant’s arguments are provided at the end of each maintained rejection.
Applicant’s arguments, see pages 12-16, filed 11/21/25, with respect to the rejections of claims 1-2, 4-7, 10, and 13-19 under 35 USC 103 have been fully considered and are persuasive. Therefore, the rejections documented in the Non-Final mailed on 8/21/25 have been withdrawn. However, upon further consideration, new grounds of rejections necessitated by claim amendments are made in this Final Office Action.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 4-7, 10, and 13-19 remain/are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims have been evaluated using the 2019 Revised Patent Subject Matter Eligibility Guidance (see Federal Register Vol. 84, No. 4 Monday, January 7, 2019).
This rejection is revised/updated in response to claim amendments filed 11/21/25.
Step 1: The claim is directed to the statutory category of a process.
Step 2A, prong one: The claim recites a judicial exception.
Claim 1 recites “determining whether a subject has a C1 subtype of colorectal cancer” with active steps of “determining”, “comparing”, and “identifying”. These limitations are abstract mental processes (see MPEP 2106.04(a)(2)(III)) that are performed within the mind.
Step 2A, prong two: The judicial exception is not integrated into a practical application.
Claims 1-2, 4-7, 10, and 13-19 recite extra-solution, data-gathering limitations at high levels of generality. Additionally, the claims are not directed to a particular treatment or prophylaxis (see MPEP 2106.04(d)(2)). Amended claim 1 recites additional extra-solution, data-gathering steps of BCL9 contacting with antibody.
Step 2B: The claim does not provide an inventive concept.
MPEP 2106.05(d)):
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity:
• i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S.
at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health
Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir.
2017);
• ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs.
Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir.
2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115
USPQ2d 1152, 1157 (Fed. Cir. 2015);
• iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78,
115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123
USPQ2d at 1088 (Fed. Cir. 2017);
• iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v.
Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
• v. Analyzing DNA to provide sequence information or detect allelic
variants, Genetic Techs. Ltd., 818 F.3d at 1377, 118 USPQ2d at 1546;
• vi. Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119
USPQ2d at 1375;
• vii. Amplifying and sequencing nucleic acid sequences, University of Utah
Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d
1241, 1247 (Fed. Cir. 2014); and
• viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d
at 1247.
The claims end with the judicial exception. Additionally, methods of determining colorectal cancer subtypes based upon gene expression have been performed before and are not inventive (Sadanandam et al. (2015; US 2015/0354009 A1; USPGPub citation 1 in IDS filed 3/16/22; and Marisa et al. (2013; NPL citation 53 in IDS filed on 7/22/25; “Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value”; PLoS Med. 2013;10(5):e1001453. doi: 10.1371/journal.pmed.1001453). Additionally, contacting the sample with an anti-B-Cell Lymphoma 9 Protein (anti-BCL9) antibody to identify a level of BCL9 protein in tumor cells is a well-understood, routine, and conventional technique in the field (Takada et al. 2012; NPL citation 71 in IDS filed on 7/22/25; “Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling. Sci Transl Med. 2012 Aug 22;4(148):148ra117. doi: 10.1126/scitranslmed.3003808).
For the reasons set forth above, claims 1-2, 4-7, 10, and 13-19 are not directed to patent eligible subject matter.
Applicant’s Arguments
Applicant argues that “Independent claim 1 is eligible under 35 U.S.C. §101 for similar reasons to claim 3 of Example 29 in the ‘Examples: Abstract Ideas’ guidance published by the USPTO in combination with the 2015 Interim Eligibility Guidelines. Claim 3 of Example 29 is reproduced below for reference: [excerpt]… Claim 3 of the guidance is directed to a process (Step 1: YES), and is directed to a judicial exception because it recites a correlation and critical thinking step (Step 2A: YES). However, when the claim is analyzed as a whole, it is clear that detecting using a porcine anti-JUL-1 antibody is an unconventional step at the time the application was filed, and there was no evidence that porcine antibodies were routinely or conventionally used to detect human proteins such as JUL-1. Thus, the claim is directed to more than a mere instruction to apply the correlation and critical thinking step using well-understood, routine, or conventional techniques in the field. Therefore, claim 3 of the guidance as a whole amounts to significantly more than the exception alone and is eligible for patenting under 35 U.S.C. §101 (Step 2B: YES). Independent claim 1 of the present application is similarly eligible for patenting under 35 U.S.C. §101” (Remarks 11/21/25, last paragraph of page 9 – third paragraph of page 10; emphasis added).
Response to Applicant’s Arguments
The Examiner respectfully disagrees with the assertion that “independent claim 1 of the present application is similarly eligible”. Contacting the sample with an anti-B-Cell Lymphoma 9 Protein (anti-BCL9) antibody to identify a level of BCL9 protein in tumor cells is a well-understood, routine, and conventional technique in the field (Takada et al. 2012; NPL citation 71 in IDS filed on 7/22/25; “Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling. Sci Transl Med. 2012 Aug 22;4(148):148ra117. doi: 10.1126/scitranslmed.3003808), and amounts to a mere extra-solution, data-gathering limitation intended to gather information for the judicial exception.
The applicant’s comparison to claim 3 of Example 29 in the ‘Examples: Abstract Ideas’ guidance published by the USPTO in combination with the 2015 Interim Eligibility Guidelines is not applicable to the instantly claimed limitations. Within Example 29, the inventive aspect is the porcine antibody detection of human proteins, which was unconventional and not routine. However, the instant use of anti-BCL9 antibody is well-known in the art (see Takada et al.) and is not inventive. Thus, independent claim 1 is not eligible under 35 U.S.C. §101.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 4-7, 10, and 14-19 are rejected under 35 U.S.C. 103 as being unpatentable over Sadanandam et al. (2015; US 2015/0354009 A1; USPGPub citation 1 in IDS filed 3/16/22) in view of Takada et al. (2012; NPL citation 71 in IDS filed on 7/22/25; “Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling. Sci Transl Med. 2012 Aug 22;4(148):148ra117. doi: 10.1126/scitranslmed.3003808) and Kalluri (2016; NPL citation U in PTO-892 filed 8/21/25; "The biology and function of fibroblasts in cancer"; Nat Rev Cancer 16, 582-598; https://doi.org/10.1038/nrc.2016.73).
This new 103 rejection is necessitated by claim amendments filed 11/21/25.
(i) Sadanandam et al. teaches limitations relevant to claims 1-2, 4, and 14-19.
Relevant to claim 1, Sadanandam et al. “relates to gene sets, the expression levels of which are useful for classifying colorectal tumors and predicting disease-free prognosis and response of patients to specific therapies that are either novel or currently available in the clinics for colorectal cancer patients” (Abstract).
The instant application discloses that identifying an elevated expression level of at least one C1 subtype-associated gene in the test sample as compared to the expression level of the C1 subtype-associated gene in a reference sample, wherein the C1 subtype-associated gene comprises a gene associated with wound healing, tissue remodeling, or neuron projection, thereby determining that the subject has a C1 subtype of colorectal cancer (CRC) (page 2, paragraph 0006 of instant Specification). The instant application also discloses that Fibroblast Activation Protein (FAP) is involved in wound healing (page 46, paragraph 00135 of instant Specification).
Further relevant to claim 1, Sadanandam et al. teaches “an in-vitro method for the prognosis of disease-free survival of a subject suffering from colorectal cancer or suspected of suffering therefrom… the method comprising (i) providing a biological sample from said subject comprising colorectal cancer cells or suspected to compromise colorectal cancer cells” (page 1, paragraphs 0008-0009). This teaching reads on claim 1 obtaining a test sample from a subject having or at risk of having CRC.
Sadanandam et al. further teaches “(ii) measuring the expression level of one or a combination of genes selected from the group of genes listed in Table 2” (page 1, paragraph 0010). As discussed above, the instant application regards elevated FAP gene expression as associated with the C1 subtype. Sadanandam et al. Table 2 on page 6 includes elevated FAP expression within the Stem-like CRC subtype. Thus, Sadanandam et al. teachings read on claim 1 determining the expression level of at least one C1 subtype-associated gene in the test sample; comparing the expression level of the C1 subtype-associated gene in the test sample with the expression level of the C1 subtype-associated gene in a reference sample; and identifying an elevated expression level of at least one C1 subtype-associated gene in the test sample as compared to the expression level of the C1 subtype-associated gene in a reference sample, wherein the C1 subtype-associated gene comprises a gene associated with wound healing.
Further relevant to claim 1, Sadanandam et al. teaches “(iii) classifying said biological sample as ‘Stem-like’” (page 1, paragraph 0011). As discussed above, the Sadanandam et al. “Stem-like” CRC subtype exhibits elevated FAP expression. The instant application regards elevated FAP gene expression as associated with the C1 subtype. Thus, Sadanandam et al. teaches determining that the subject has a C1 subtype of colorectal cancer (CRC).
Relevant to claim 2, Sadanandam et al. teaches "(ii) measuring the expression level of one or a combination of genes selected from the group of genes listed in Table 2" (paragraph 0010) and "According to another embodiment, expression of a gene of interest is considered elevated when compared to a healthy control if the relative mRNA level of the gene of interest is greater than 2 fold of the level of a control gene mRNA" (paragraph 0165).
These teachings read on claim 2 wherein the method comprises identifying an elevated expression level of at least two C1 subtype-associated genes in the test sample as compared to the expression level of the C1 subtype-associated gene in a reference sample; or wherein the method comprises identifying an elevated expression level of at least three C1 subtype-associated genes in the test sample as compared to the expression level of the C1 subtype-associated gene in a reference sample.
Relevant to claim 4, Sadanandam et al. teaches “(ii) measuring the expression level of one or a combination of genes selected from the group of genes listed in Table 2” (page 1, paragraph 0010). As discussed above, the instant application regards elevated FAP gene expression as associated with the C1 subtype. Sadanandam et al. Table 2 on page 6 includes elevated FAP expression within the Stem-like CRC subtype. Thus, Sadanandam et al. teachings read on claim 4 wherein the C1 subtype-associated gene comprises fibroblast activating protein (FAP).
Relevant to claim 14, Sadanandam et al. teaches "Preferably a biological sample is obtained from a tissue biopsy" (paragraph 0160). This teaching reads on claim 14 wherein the test sample is obtained from a CRC tissue.
Relevant to claim 15, Sadanandam et al. teaches "Preferably measuring the expression level of genes in methods of the present invention is obtained by a method selected from the group consisting of: (a) detecting RNA levels of said genes, and/or (b) detecting a protein encoded by said genes, and/or (c) detecting a biological activity of a protein encoded by said genes" (paragraph 0162).
This teaching reads on claim 15 wherein the test sample comprises… a ribonucleic acid (RNA), or an amino acid.
Relevant to claims 16-17, Sadanandam et al. teaches "According to another embodiment, expression of a gene of interest is considered elevated when compared to a healthy control if the relative mRNA level of the gene of interest is greater than 2 fold of the level of a control gene mRNA" (paragraph 0165).
This teaching reads on claim 16 wherein the reference sample is obtained from healthy normal tissue or CRC tissue; and claim 17 wherein the reference sample is obtained from healthy normal tissue from the same individual as the test sample or one or more healthy normal tissues from different individuals.
Relevant to claim 18, Sadanandam et al. teaches "The detecting RNA levels is obtained by any technique known in the art, such as Microarray hybridization, quantitative real-time polymerase chain reaction, multiplex PCR, Northern blot, InSitu Hybridization, sequencing-based methods, quantitative reverse transcription polymerase-chain reaction, RNAse protection assay or an immunoassay method" (paragraph 0163).
This teaching reads on claim 18 wherein the expression level of the C1 subtype-associated gene is detected via a gene hybridization microarray, next generation sequencing, ribonucleic acid sequencing (RNA-seq), a real time reverse transcriptase polymerase chain reaction (real time RT-PCR) assay, immunohistochemistry (IHC), or immunofluorescence.
Relevant to claim 19, Sadanandam et al. teaches "As used herein the terms 'subject' or 'patient' are well-recognized in the art, and, are used interchangeably herein to refer to… most preferably, a human" (paragraph 0054).
This teaching reads on claim 19 wherein the subject is human.
(ii) Sadanandam et al. is silent to specifics regarding BCL9 expression relevant to claims 1 and 10. However, these limitations were known in the prior art and taught by Takada et al.
Relevant to claim 1, Takada et al. teaches “Immunoblotting and coimmunoprecipitation. For Western blotting, performed as described [citation], the following primary antibodies were used: BCL9 (6109) [citation], BCL9 (ab37305, Abcam)…” (page 10, right column, paragraph 2).
This teaching reads on claim 1 contacting the sample with an anti-B-Cell Lymphoma 9 Protein (anti-BCL9) antibody to identify a level of BCL9 protein in tumor cells of the sample.
Further relevant to claim 1, Takada et al. teaches "It is important to note that BCL9 is absent from the normal cells from which tumors originate [citation]" (page 1, column 2, paragraph 2).
This teaching reads on claim 1 identifying an elevated level of nuclear BCL9 in tumor cells from the test sample as compared to…cells from the test sample.
Relevant to claim 10, Takada et al. teaches "These PBMC and fibroblast data highlight that the antiproliferative activity of SAH-BCL9B specifically depends on the expression of BCL9 and β-catenin and their colocalization in the nuclear compartment" (page 6, paragraph 1).
This nuclear compartment localization, or punctuate pattern, reads on claim 10 wherein the nuclear BCL9 expression in tumor cells exhibits a punctuate pattern.
(iii) Sadanandam et al. in view of Takada et al. is silent to specifics regarding stromal cells relevant to claims 1 and 5-7. However, these limitations were known in the prior art and taught by Kalluri.
Relevant to claims 1 and 5, Kalluri teaches "As tumours grow and become invasive, the stromal content also increases" (page 587, column 1, paragraph 2).
This teaching reads on claim 1 stromal cells from the test sample; and claim 5 further comprising identifying an elevated level of stromal cells in the test sample as compared to a reference sample, as CRC tumor cells would have an elevated level of stromal cells as compared to a non-CRC reference sample.
Relevant to claim 6, Kalluri teaches "Without question, fibroblasts are the most versatile and extensively studied cells in vitro owing to their ease of isolation and culture. They survive severe stress and can be live-cultured from human post-mortem tissue [citation]. In the context of an unforgiving, highly dynamic and injurious tissue microenvironment, including damage induced by chemotherapy or radiotherapy, CAFs [cancer-associated fibroblasts] may represent a resistant stromal cell type that could participate in tumour relapse" (page 582, column 2, paragraph 2).
This teaching reads on claim 6 wherein the stromal cell comprises a fibroblast.
Relevant to claim 7, Kalluri teaches "Fibroblasts cultured from the site of a healing wound or from fibrotic tissue secrete higher levels of ECM constituents and proliferate more than their counterparts isolated from healthy organs [citations]. Such increased activity is referred to as activation [citation] (FIG. 1). Once activated, their functions include synthesizing ECM, generating cytokines and chemokines, recruiting immune cells and exerting physical forces to modify tissue architecture [citations]" (page 585, column 1, paragraph 1).
This teaching reads on claim 7 further comprising identifying an elevated level of stromal cells in the test sample as compared to the level of immune cells in the test sample.
(iv) Although Sadanandam et al. does not explicitly teach the Takada et al. BCL9 expression or Kalluri stromal cells, it would have been prima facie obvious to the skilled artisan. It is noted that Sadanandam et al., Takada et al., and Kalluri are analogous disclosures to the instant cancer biology field.
The skilled artisan would have been motivated to combine the analogous art. Takada et al. teaches “To examine the phenotypic consequences of pharmacologic disruption of the β-catenin/BCL9/B9L complex, we conducted cellular proliferation, angiogenesis, and migration assays based on our previous findings that these key physiologic processes are regulated by BCL9/β-catenin in CRC and MM cells” (page 4, column 2, paragraph 2).
Thus, the skilled artisan would have been motivated to examine the Takada et al. BCL9 expression within the Sadanandam et al. methodology because Takada et al. teaches that BCL9 molecular interactions are critical within CRC physiological processes and pathogenesis.
Kalluri teaches that elevated stromal cells, like cancer-associated fibroblasts, are characteristic of tumors and may participate in “tumour relapse”. Thus, the skilled artisan would have been motivated to examine the Kalluri stromal cells within the Sadanandam et al. methodology in order to characterize the pathogenically-important cell populations.
The skilled artisan would have a reasonable expectation of success based on the disclosures of Sadanandam et al. in view of Takada et al. and Kalluri, as discussed in the preceding paragraphs.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Sadanandam et al. (2015; US 2015/0354009 A1; USPGPub citation 1 in IDS filed 3/16/22) in view of Takada et al. (2012; NPL citation 71 in IDS filed on 7/22/25; “Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling. Sci Transl Med. 2012 Aug 22;4(148):148ra117. doi: 10.1126/scitranslmed.3003808) and Kalluri (2016; NPL citation U in PTO-892 filed 8/21/25; "The biology and function of fibroblasts in cancer"; Nat Rev Cancer 16, 582-598; https://doi.org/10.1038/nrc.2016.73), as applied to claims 1-2, 4-7, 10, and 14-19 above, and further in view of Zhang et al. (2018; NPL citation V in PTO-892 filed 8/21/25; "The lncRNA NEAT1 activates Wnt/B-catenin signaling and promotes colorectal cancer progression via interacting with DDX5"; J Hematol Oncol 11, 113 (2018); https://doi.org/10.1186/s13045-018-0656-7) and Naganuma et al. (2012; NPL citation 58 in IDS filed on 7/22/25; “Alternative 3'-end processing of long noncoding RNA initiates construction of nuclear paraspeckles”; EMBO J. 2012 Oct 17;31(20):4020-34. doi: 10.1038/emboj.2012.251).
The teachings of Sadanandam et al. in view of Takada et al. and Kalluri are applied to instantly rejected claim 13 as they were previously applied to claims 1-2, 4-7, 10, and 14-19 as rendering obvious a method of determining whether a subject has a C1 subtype of CRC.
Sadanandam et al. in view of Takada et al. and Kalluri is silent to specifics regarding BCL9 expression localization adjacent to paraspeckles or co-localization adjacent to paraspeckle proteins relevant to claim 13. However, these limitations were known in the prior art and taught by Zhang et al. and Naganuma et al.
(i) Relevant to claim 13, Takada et al. Abstract teaches "Therefore, we have directed our efforts toward blocking the interaction of β -catenin with B cell lymphoma 9 (BCL9), a co-activator for β -catenin–mediated transcription that is highly expressed in tumors but not in the cells of origin. BCL9 drives β -catenin signaling through direct binding mediated by its a-helical homology domain 2. We developed a stabilized a helix of BCL9 (SAH-BCL9), which we show targets β -catenin, dissociates native β -catenin/BCL9 complexes, selectively suppresses Wnt transcription, and exhibits mechanism-based antitumor effects. SAH-BCL9 also suppresses tumor growth, angiogenesis, invasion, and metastasis in mouse xenograft models of Colo320 colorectal carcinoma…"
Further relevant to claim 13, Takada et al. teaches that “Several coactivators for Wnt/β-catenin transcription have been identified and include… B cell lymphoma 9 (BCL9)" (page 1, column 1, paragraph 2).
Further relevant to claim 13, Takada et al. teaches "These PBMC and fibroblast data highlight that the antiproliferative activity of SAH-BCL9B specifically depends on the expression of BCL9 and β-catenin and their colocalization in the nuclear compartment" (page 6, paragraph 1).
Thus, Takada et al. teaches that BCL9 is localized to the nuclear compartment and is a co-activator of Wnt/β-catenin transcription in colorectal cancer cells.
(ii) However, Takada et al. is silent to paraspeckles.
Zhang et al. Abstract teaches that "The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC)." Additionally, Zhang et al. teaches that "NEAT1 is an essential component of nuclear paraspeckles [citation], which contain ribonucleoprotein complexes formed around NEAT1 [citation]" (page 9, column 2, paragraph 2). Zhang et al. further teaches that "Our results suggest that NEAT1 promotes CRC tumor growth and metastasis by stabilizing the DDX5 protein, thereby activating β-catenin gene transcription" (page 9, first paragraph of "Discussion" section).
Thus, Zhang et al. teaches that NEAT1 is an essential component of nuclear paraspeckles and that NEAT1 indirectly activates Wnt/β-catenin signaling though DDX5 interaction.
(iii) However, Takada et al. and Zhang et al. are silent to BCL9 localization adjacent to paraspeckles and co-localization adjacent to one or more paraspeckle proteins.
Naganuma et al. teaches that "Paraspeckles are recently discovered nuclear bodies that are usually detected in cultured cell lines as a variable number of foci found in close proximity to the nuclear speckles. Paraspeckles contain characteristic RNA-binding proteins, including paraspeckle protein 1 (PSPC1), RBM14, NONO, CPSF6, and SFPQ" (page 4020, column 2, paragraph 3). Additionally, Naganuma et al. teaches that "Several of the new PSPs [paraspeckle proteins] are likely to be DNA-binding proteins that are involved in transcriptional control. This finding raises the possibility that paraspeckles may integrate tightly coupled transcription and post-transcriptional events" (page 4029, column 2, paragraph 1).
Thus, Naganuma et al. teaches that paraspeckles contain proteins that are implicated in transcriptional regulation (including the instant NONO and SFPQ), and that paraspeckles integrate tightly coupled transcription and post-transcriptional events.
(iv) It would have been prima facie obvious to the skilled artisan to examine the Zhang et al. and Naganuma et al. paraspeckle limitations within the methodology rendered obvious by Sadanandam et al. in view of Takada et al. and Kalluri. It is noted that Sadanandam et al., Takada et al., Kalluri, Zhang et al., and Naganuma et al. are all analogous disclosures to the instant cancer biology field.
The skilled artisan would have been motivated to combine the analogous art.
Takada et al. teaches that BCL9 and β-catenin co-localize to the nuclear compartment. Zhang et al. teaches that NEAT1 paraspeckles modulate β-catenin transcriptional activity through a co-factor. These teachings, when considered together, suggest that Wnt/β-catenin co-activators, such as BCL9, may be spatially associated with paraspeckle structures that regulate the same pathway.
A motivation to combine the teachings is provided by the known role of paraspeckles as nuclear structures that tightly couple transcription and post-transcriptional events. Given that BCL9 is a nuclear β-catenin co-activator in CRC and NEAT1 paraspeckles modulate Wnt/β-catenin signaling, a skilled artisan would have been motivated to examine whether BCL9 is enriched adjacent to paraspeckles in order to better understand this pathogenic pathway.
The methods for determining subnuclear localization (e.g., immunofluorescence, confocal microscopy, etc.) were well-known and routinely used for nuclear proteins (see Naganuma et al. microscopy images). Therefore, the skilled artisan would have had a reasonable expectation of success in applying such routine methods to determine whether BCL9 is enriched adjacent to paraspeckles. Thus, the claimed localization of BCL9 adjacent to paraspeckles would have been obvious to the skilled artisan in view of the combined teachings.
The skilled artisan would have a reasonable expectation of success based on the disclosures of Sadanandam et al. in view of Takada et al. and Kalluri, and further in view of Zhang et al. and Naganuma et al. as discussed in the preceding paragraphs.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SARAH JANE KENNEDY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682