DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 29 August 2025 has been entered.
Comments
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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.
Claims 122-124, 126, 142-145, 147-149, and 151-159 are pending and examined in the instant Office action.
Even though the claims recite judicial exceptions, the claims are subject matter eligible because the claims recite the practical application of administering particular treatments for cancer.
Withdrawn Rejections
The prior art rejections are withdrawn in view of amendments filed to the instant set of claims on 29 August 2025.
Claim Rejections - 35 USC § 112(d) - Does not further limit
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 142 is 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.
In claim 142, the limitation “the discriminating human gene set comprises at least five human genes selected from the group consisting of SCNN1A, CDX1, KCNK15, PRKCG, KRT7, NKD2, GPR158, CLDN3, and ZNF683” is already in independent claim 122. Consequently, dependent claim 142 does not further limit independent claim 122.
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 § 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.
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.
The following rejection is newly applied:
Claim(s) 122-124, 126, 142-145, 147-149, and 151-159 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vogelstein et al. [WO 2019/067092 A1] in view of Pyeon et al. [WO 2017/070709 A1] in view of Saetrom et al. [US PGPUB 2018/0305689 A1] in view of Gulley [Experimental & Molecular Medicine, volume 47, 2015; article e134; on IDS].
Claim 122 is drawn to a method for discriminating between a first cancer condition and a second cancer condition in a subject afflicted with a types of cancer. The first cancer condition is associated with an EBV infection and the second cancer condition is associated with an EBV-free status. The method comprises obtaining a dataset for the subject. The dataset comprises a plurality of mRNA abundance values. Each respective abundance value in the plurality of mRNA abundance values quantifies a level of expression of a corresponding human gene in a cancerous tissue from the subject. The method requires that the discriminating human gene set comprises at least five human genes selected from the group consisting of SCNN1A, CDX1, KCNK15, PRKCG, KRT7, NKD2, GPR158, CLDN3, and ZNF683. The method comprises inputting the dataset to a classifier trained to discriminate between at least the first cancer condition and the second cancer condition based on mRNA abundance values for the discriminating human gene set in a cancerous tissue of a subject. The comprises obtaining a classifier result that determines a cancer condition of the subject. The method comprises treating the subject for the type of cancer with a first therapy tailored for the first cancer condition or a second therapy tailored for the second cancer condition.
Claim 126 is further limiting wherein the cancer is gastric cancer associated with EBV.
Claims 142 and 144 recite a list of discriminating genes.
Claims 143 and 152 recite that the cancer is gastric cancer.
The document of Vogelstein et al. studies methods and materials for assessing and treating cancer [title]. Paragraph 459 of Vogelstein et al. teaches that the cancer condition may be EBV related or not EBV related. Paragraph 466 of Vogelstein et al. teaches analyzing biomarker datasets for differential genetic expression patterns. Paragraphs 390-391 of Vogelstein et al. teaches the use of machine learning in the form of SVM to classify cancer types (e.g. cancer of a particular original versus cancer not from the particular origin) of different potential cancer samples based on abundances of biomarker genetic expression patterns. Paragraph 773 of Vogelstein et al. teaches a list of different cancer therapies.
While Vogelstein et al. teaches machine learning to classify between different types of cancers, Vogelstein et al. does not teach using machine learning to classify between an EBV related cancer and its corresponding EBV-free cancer.
While Vogelstein et al. teaches lists of different types of treatments, Vogelstein et al. does not teach a first treatment for an EBV-related cancer and a second treatment for a corresponding EBV-free cancer.
Vogelstein et al. does not teach basing classification on mRNA abundance values from human genes.
Vogelstein et al. does not teach the discriminating genes. Vogelstein et al. does not teach associating gastric cancer with EBV.
The document of Pyeon et al. studies prognosis and treatment of squamous cell carcinomas [title]. Page 2, line 24 to page 3, line 17 of Pyeon et al. teaches classifying human papilloma virus in cancerous tissue by abundance values of CXCL14 mRNA.
Vogelstein et al. and Pyeon et al. do not teach the discriminating genes. Vogelstein et al. and Pyeon et al. do not teach associating gastric cancer with EBV.
The document of Saetrom et al. studies saRNA compositions and methods of use [title]. Paragraph 329 of Saetrom et al. teaches that the analysis is applicable to gastric cancer. Paragraph 100 of Saetrom is a list comprising the discriminating genes lists in claims 142 and 144.
Vogelstein et al., Pyeon et al., and Saetrom et al. do not teach associating gastric cancer with EBV.
The document of Gulley studies genomic assays for EBV-positive gastric adenocarcinoma [title].
With regard to claim 123, paragraph 29 of Vogelstein et al. teaches colorectal cancer.
With regard to claim 124, page 562 of Vogelstein et al. teaches the significance of allele frequencies and variants. Paragraph 338 of Vogelstein et al. teaches analysis of TP53 and PIK3CA biomarkers. Paragraphs 390-391 of Vogelstein et al. teaches the use of machine learning in the form of SVM to classify cancer types of different potential cancer samples based on abundances of biomarker genetic expression patterns.
With regard to claims 145 and 153-154, page 562 of Vogelstein et al. teaches the significance of allele frequencies and variants. Paragraph 338 of Vogelstein et al. teaches analysis of TP53 and PIK3CA biomarkers. Paragraphs 390-391 of Vogelstein et al. teaches the use of machine learning in the form of SVM to classify cancer types of different potential cancer samples based on abundances of biomarker genetic expression patterns. Page 117 of Vogelstein et al. teaches analysis of gastric cancer.
With regard to claim 147-149 and 155-156, paragraph 805 of Vogelstein et al. teaches cancer therapy using immune checkpoint inhibitors. Paragraph 773 of Vogelstein et al. teaches cancer therapy in the form of chemotherapy with cisplatin, carboplatin, or paclitaxel.
With regard to claim 151, paragraphs 390-391 of Vogelstein et al. teach the use of machine learning in the form of SVM to classify cancer types of different potential cancer samples based on abundances of biomarker genetic expression patterns. Paragraph 257 of Vogelstein et al. studies analyzing a plurality of patients. Page 2, line 24 to page 3, line 17 of Pyeon et al. teaches classifying human papilloma virus in cancerous tissue by abundance values of CXCL14 mRNA.
With regard to claim 157, paragraphs 390-391 of Vogelstein et al. teach the use of machine learning in the form of SVM to classify cancer types of different potential cancer samples based on abundances of biomarker genetic expression patterns.
With regard to claims 158-159, paragraphs 532 and 542 of Vogelstein et al. teach sequencing, alignment, and analysis of mRNA compared to a reference DNA genome for genetic analysis. Paragraph 466 of Vogelstein et al. teaches analyzing biomarker datasets for differential genetic expression patterns based on genetic variants. Page 2, line 24 to page 3, line 17 of Pyeon et al. teaches classifying human papilloma virus in cancerous tissue by abundance values of CXCL14 mRNA.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the use of machine learning to classify cancer of Vogelstein et al. based on origin by use of the origin being either EBV or EBV-free because it is obvious to try the generic machine learning algorithms that are robustly applicable to different types of cancers to specifically apply to cancers dependent on whether the origin is EBV or EBV-free [paragraphs 390-391 of Vogelstein et al.].
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the cancer treatments of Vogelstein et al. based on origin by use of the origin being either EBV or EBV-free because it is obvious to substitute known elements in the prior art to yield a predictable result. In this instance, the cancer treatments of Vogelstein et al. are robust and generally applicable independent of whether the cancer has an EBV origin or an EBV-free origin.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the classification of cancer type (i.e. EBV or EBV-free) of Vogelstein et al. by use of the classification of HPV versus HPV-free cancer using human mRNA abundance values of Pyeon et al. wherein the motivation would have been that Pyeon et al. gives additional genetic data from which to classify cancer type [page 2, line 24 to page 3, line 17 of Pyeon et al.]. There would have been a reasonable expectation of success in combining Vogelstein et al. and Pyeon et al. because both studies analogously pertain to the classifying cancer type as virus versus virus-free.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the cancer analysis of Vogelstein et al. and the classification of cancer as being virus versus virus-free using human mRNA abundances of Pyeon et al. by use of the genes of Saetrom et al. because it is obvious to substitute known elements in the prior art to yield a predictable result. In this instance, the genes of Saetrom et al. are an alternative to the genes of Vogelstein et al. There would have been a reasonable expectation of success in combining Vogelstein et al., Pyeon et al., and Saetrom et al. because the machine learning as applied to cancer of Vogelstein et al. is robust and generally applicable to genes, including the genes of Pyeon et al. and Saetrom et al. In addition, both Vogelstein et al. and Saetrom et al. are analogously applicable to gastric cancer.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the cancer analysis of Vogelstein et al., and the genes of Saetrom et al. by use of the cancer classification using human mRNA abundances of Pyeon et al. to be applicable to gastric cancer related to EBV of Gulley because it is obvious to substitute known elements in the prior art to yield a predictable result. In this instance, the gastric cancer related to EBV of Gulley is an alternative to the cancers of Vogelstein et al. There would have been a reasonable expectation of success in combining Vogelstein et al. and Gulley because the machine learning as applied to cancer of Vogelstein et al. is robust and generally applicable to cancers, including the EBV-positive gastric cancer of Gulley. In addition, there would have been a reasonable expectation of success in combining Saetrom et al. and Gulley because both studies are analogously applicable to gastric cancer.
Response to Arguments
Applicant's arguments filed 29 August 2025 have been fully considered but they are not persuasive.
Applicant has no arguments specific to Vogelstein et al. and Pyeon et al.
Applicant’s central argument is that one of skill in the art would require undue experimentation to choose the recited human genes from the thousands of human genes listed in paragraph 100 of Saetrom et al. This argument would be persuasive if applicant uses CLOSED language to state that the human genes CONSIST of ONLY the human genes recited in the claims. Since applicant, uses OPEN language to require that the gene COMPRISE five of the recites human genes, as long as the list includes the recited genes, paragraph 100 of Saetrom et al. can list an unlimited number of other genes, and paragraph 100 of Saetrom still meets the intended limitation of the claims.
Applicant also argues that the intent of Saetrom et al. pertains to regulation of gene expression and not classification of cancer. This argument is not persuasive because paragraph 329 of Saetrom et al. teaches that the genetic study pertains to cancer, including gastric cancer. While paragraph 329 of Saetrom includes about 200 other cancers, the document of Gulley has been added to the rejection statement to emphasize an association between gastric cancer and EBV.
E-mail Communications Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Russell Negin, whose telephone number is (571) 272-1083. This Examiner can normally be reached from Monday through Thursday from 8 am to 3 pm and variable hours on Fridays.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Larry Riggs, Supervisory Patent Examiner, can be reached at (571) 270-3062.
/RUSSELL S NEGIN/Primary Examiner, Art Unit 1686 9 September 2025
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