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 1-4 and 6-19 are pending and under examination. Claims 5 and 20-23 are cancelled. Claims 1, 6-8, and 16-17 are amended.
Response to Amendment
The Amendment filed 2/25/26 has been entered. Claims 1-4 and 6-19 are pending. Applicant’s amendments to claims 1, 6-8, and 16-17, and specification have overcome the objections, 112(b), and 102 rejections previously set forth in the Non-Final Office Action mailed 11/18/25.
The 2/25/26 submission of the certified English translation of foreign priority document KR10-2020-0056699 is acknowledged. The priority date is determined to be 5/12/20.
Response to Arguments
Applicant’s arguments, see pages 10-11, filed 2/25/26, with respect to the rejections of claims 1-4 and 6-19 under 35 USC 101 have been fully considered and are found persuasive. Therefore, the rejections documented in the Non-Final mailed 11/18/25 have been withdrawn. However, upon further consideration, new grounds of 112(b), 112(d), 101, and 103 rejections necessitated by claim amendments are made in this Final Office Action.
Claim Rejections - 35 USC § 112 – Indefiniteness
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 and 11-13 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
This new 112(b) rejection is necessitated by claim amendments filed 2/25/26.
Claim 2 recites the limitation "the prognosis of breast cancer" in line 1. Claim 11 recites the limitation "the prognosis of patients’ breast cancer" in line 3. There is insufficient antecedent basis for this limitation in the claim. Amended claim 1 has removed the breast cancer prognosis limitation, leaving claims 2 and 11 recitations of “prognosis” unclear as to how the limitation relates to “a method for treating breast cancer in a breast cancer patient”.
Claims 12-13 directly or indirectly depend on claim 11 and are similarly indefinite.
Where there is a great deal of confusion and uncertainty as to the proper interpretation of the limitations of a claim, it would not be proper to reject such a claim on the basis of prior art (In re Steele).
Claim Rejections - 35 USC § 112 – Failure to 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 6 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.
This new 112(d) rejection is necessitated by claim amendments filed 2/25/26.
Claim 6 depends from claim 1, which recites “(a) measuring mRNA expression levels of immune-related genes”. Claim 6 expands upon claim 1 mRNA measurement to further include an alternative measurement through “measuring… the expression levels of the proteins encoded by the genes.” Thus, claim 6 fails to further limit claim 1 subject matter upon which claim 6 depends.
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 § 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 1-4 and 6-19 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 new 101 rejection is necessitated by claim amendments filed 2/25/26.
Step 1: The claims are directed to the statutory category of a process.
Step 2A, prong one: The claims recite a judicial exception.
Claims 1 and 16-17 recite a correlation of immune-related genes’ mRNA expression levels and breast cancer status. This genotype-phenotype correlation is a law of nature and natural phenomena (see MPEP 2106.04(b)). Claims 1 (c), 11-13, and 16-17 recite abstract mental processes through the mathematical calculations/analyses of gathered data. Per MPEP 2106.04(a)(2), Abstract Ideas include mathematical concepts and mental processes.
Step 2A, prong two: The judicial exceptions are not integrated into a practical application.
None of the claims provide any additional elements in addition to the judicial exceptions already claimed that would prevent the claims from having a pre-emptive effect on the use of the judicial exception. Claims 1-4 and 6-19 recite extra-solution and data-gathering limitations for the judicial exception. These limitations generate the input data of the judicial exceptions, with no specification of a particular treatment or prophylaxis (see MPEP 2106.04(d)(2)). The non-particular/non-specific nature of the treatment is emphasized by claim 1 (e) recitation of “an anti-cancer agent, a surgery and a radiation therapy” and no particular Specification disclosure of particular agents, surgeries, or radiation treatments/dosages/molecules.
Step 2B: The claims do 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 are directed to well-understood, routine, and conventional activities in the life science arts recited at a high-level of generality. The claimed processes are not inventive; the instant specification page 15, paragraphs 2-4 disclose “these [expression measuring] methods are known in the art”. Additionally, methods of mRNA expression-based treatments of breast cancer have been performed before and are not inventive (see Cho et al. (2018; US 2018/0216199 A1); and Zhang et al. (2019; US 2019/0112671 A1)).
For the reasons set forth above, claims 1-4 and 6-19 are not directed to patent eligible subject matter.
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, 3-4, 6-7, 9-10, and 14-19 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (2019; US 2019/0112671 A1) in view of Cho et al. (2018; US 2018/0216199 A1).
This new 103 rejection is necessitated by claim amendments filed 2/25/26.
(i) Zhang et al. teaches limitations relevant to claims 1, 3, 9, and 14-17.
Relevant to claim 1, Zhang et al. Abstract teaches “Methods of treating a patient, such as a patient with breast cancer, and methods of selecting a therapy for a patient. The methods of treating a patient may include determining one or more expression levels for a set of biomarkers from a biological sample of the patient. The biological sample may include breast cancer tissue.”
Relevant to claim 1 (c) and (e), Zhang et al. Figure 3D depicts decreased expression of instantly claimed immune-related genes PRKCB and RAC2.
Relevant to claim 1 (d), Zhang et al. Example 1 (paragraphs 0050+) teaches “Subgrouping Breast Cancer Patients Based on Immune Evasion Mechanisms” in order to “provide a better diagnostic to help guide treatments.”
Further relevant to claim 1 (d), Zhang et al. teaches that the TCGA RNA-Seq data used include both breast cancer samples and non-malignant adjacent normal tissue samples (paragraph 0060), and that the differential gene expression analyses (including those associated with Figure 3D) used the non-malignant adjacent normal tissue samples (reference breast tumor) as a comparison for differential expression.
Further relevant to claim 1 (e), Zhang et al. paragraph 0108 teaches “Potential Immunotherapies” including anti-cancer agents based upon the expression-based subgroups.
Relevant to claim 3, Zhang et al. paragraph 0074 teaches the breast cancers are selected from HER2 (HR-/HER2+), Luminal A (HR+/HER2-), Luminal B (HR+/HER2+), and TNBC.
Relevant to claim 9, Zhang et al. paragraph 0044 teaches that the “biological sample may include any tissue… collected from a patient… A cancer tissue generally may include a tumor tissue. In some embodiments, the biological tissue includes breast cancer tissue.”
Relevant to claims 14-15, Zhang et al. paragraph 0058 teaches that TRAT1, IL21R, CTLA4, and IL2RB are included within the “Full List of Immune-Related Genes” identified as important genes. Although Zhang et al. does not explicitly disclose IGHM, Zhang et al. Figure 1 teaches “Antigen Recognition and Presentation” within the context of “evasion at different levels of the cancer-immunity cycle in each cluster”. The skilled artisan would recognize that the instantly claimed Immunoglobulin Heavy Constant Mu (IGHM) plays a role in antigen recognition and would recognize that the “Ignorance” and “Lack of a Danger Signal” associated with cluster 4 would embrace IGHM, which is responsible for antigen recognition.
Relevant to claims 16-17, Zhang et al. Abstract teaches “Methods of treating a patient, such as a patient with breast cancer, and methods of selecting a therapy for a patient. The methods of treating a patient may include determining one or more expression levels for a set of biomarkers from a biological sample of the patient. The biological sample may include breast cancer tissue.”
Relevant to claims 16 (i) and 17 (i), Zhang et al. paragraph 0058 teaches that TRAT1, IL21R, CTLA4, and IL2RB are included within the “Full List of Immune-Related Genes” identified as important genes. Although Zhang et al. does not explicitly disclose IGHM, Zhang et al. Figure 1 teaches “Antigen Recognition and Presentation” within the context of “evasion at different levels of the cancer-immunity cycle in each cluster”. The skilled artisan would recognize that the instantly claimed Immunoglobulin Heavy Constant Mu (IGHM) plays a role in antigen recognition and would recognize that the “Ignorance” and “Lack of a Danger Signal” associated with cluster 4 would embrace IGHM, which is responsible for antigen recognition.
Relevant to claims 16 (v) and 17 (v), Zhang et al. paragraph 0108 teaches “Potential Immunotherapies” including anti-cancer agents based upon the expression-based subgroups.
(ii) Zhang et al. is silent to limitations relevant to mRNA expression levels (claims 1, 6-7, and 16-19); Tumor Node Metastasis (claims 4, 10, and 16-17); and breast cancer prognostic risk score (claims 16-17). However, these limitations were known in the prior art and taught by Cho et al.
Relevant to claim 1 (a) – (b), Cho et al. paragraph 0003 teaches “a method for predicting the prognosis of breast cancer, and more particularly to a method for predicting the prognosis of breast cancer, the method comprising steps of: (a) measuring mRNA expression level of at least one proliferation-related genes selected from the group consisting of… an immune-related gene from the biological sample obtained from the breast cancer patient; (b) normalizing the mRNA expression level measured in the step (a)”.
Relevant to claim 4, Cho et al. paragraph 0063 teaches that the breast cancer corresponds to pN0 or pN1 according to the TNM stage.
Relevant to claims 6-7 and 18-19, Cho et al. paragraphs 0071-0073 teach methods for measuring the expression levels of mRNA of the genes including probes, microarrays, PCR, RT-PCR, qRT-PCR, real-time PCR, northern blot, DNA chips and RNA chips.
Relevant to claim 10, Cho et al. paragraph 0088 teaches “The pNl refers a stage in which micrometastases in one to three ipsilateral axillary lymph nodes are found” and paragraph 0087 teaches “The higher the pN level is, the more metastasis of tumor cell to the lymph nodes has occurred. So the effectiveness of chemotherapy can be determined to be high because the prognosis of breast cancer was poor.”
Relevant to claims 16 and 17 (i) – (iii), Cho et al. paragraph 0003 teaches “a method for predicting the prognosis of breast cancer, and more particularly to a method for predicting the prognosis of breast cancer, the method comprising steps of: (a) measuring mRNA expression level of at least one proliferation-related genes selected from the group consisting of… an immune-related gene from the biological sample obtained from the breast cancer patient; (b) normalizing the mRNA expression level measured in the step (a); and (c) predicting the prognosis of breast cancer”.
Relevant to claims 16 and 17 (iii), Cho et al. Equations 1 and 2 relating to the BCT score read on the instant formulae, wherein the Cox Regression estimates, normalized gene expression level, and TNM status are included within the calculations.
Relevant to claims 16 and 17 (iv) – (v), Cho et al. paragraph 0180 teaches “As the BCT [breast cancer test] score increases, the possibility of cancer recurrence, metastasis or metastatic recurrence within 10 years is increased.” The skilled artisan would thus find claims 16 and 17 (iv) – (v) diagnosis and treatment obvious, as Cho et al. paragraph 0082 teaches “patients with the high effectiveness of chemotherapy are those who are predicted to have a poor prognosis of the breast cancer patient (i.e., who are expected to have a ‘bad prognosis’ in the future), and require additional chemotherapy after surgery because of the high probability of metastasis, recurrence or metastatic recurrence within 10 years.”
(iii) Although Zhang et al. is silent to the Cho et al. limitations, it would have been prima facie obvious to the skilled artisan. Zhang et al. and Cho et al. are analogous disclosures to the instant breast cancer genomics invention.
The skilled artisan would have been motivated to combine the analogous disclosures. The skilled artisan would have been motivated to include the Cho et al. mRNA expression levels within the Zhang et al. methodology because Cho et al. paragraph 0072 teaches that mRNA expression levels enable a “quantitative detection of the expression level of the gene of interest” and “can be measured by any method performed in the art to measure the expression level of the gene” (paragraph 0071), thereby allowing widespread applications for quantification of genes of interest.
The skilled artisan would further be motivated to include the Cho et al. Tumor Node Metastasis within the Zhang et al. methodology because Cho et al. paragraph 0006 teaches that this classification is common within breast cancers and that the classification is a significant factor within prognostic prediction models (paragraphs 0168-0169).
The skilled artisan would further be motivated to include the Cho et al. breast cancer prognostic risk score within the Zhang et al. methodology because Cho et al. paragraph 0192 teaches that their prognoses accurately predict breast cancer outcomes and “can be used for the purpose of presenting information on the direction of breast cancer treatment in the future, and is highly available in industry”.
The skilled artisan would have a reasonable expectation of success based on the disclosures of Zhang et al. in view of Cho et al., as discussed in the preceding paragraphs.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (2019; US 2019/0112671 A1) in view of Cho et al. (2018; US 2018/0216199 A1), as applied to claims 1, 3-4, 6-7, 9-10, and 14-19 above, and further in view of Baker et al. (2016; US 2016/0222463 A1).
The teachings of Zhang et al. in view of Cho et al. are applied to instantly rejected claim 8 as they were previously applied to claims 1, 3-4, 6-7, 9-10, and 14-19 as rendering obvious a method. Zhang et al. in view of Cho et al. is silent to claim 8 specifics of measuring the expression levels of antibodies that specifically bind to the proteins. However, this limitation was known in the prior art and taught by Baker et al.
Relevant to claim 8, Baker et al. paragraph 0002 teaches “The present invention relates to biomarkers associated with breast cancer prognosis. These biomarkers include coding transcripts and their expression products, as well as non-coding transcripts, and are useful for predicting the likelihood of breast cancer recurrence in a breast cancer patient.”
Further relevant to claim 8, Baker et al. paragraph 0091 teaches immunohistochemistry and antibody-mediated detection of expression levels of gene of interest gene products.
Although Zhang et al. in view of Cho et al. does not explicitly disclose the Baker et al. antibody limitations, it would have been prima facie obvious to the skilled artisan. It is noted that Zhang et al., Cho et al., and Baker et al. are analogous disclosures to the instant breast cancer genomics invention.
The skilled artisan would have been motivated to combine the analogous disclosures. Baker et al. paragraph 0091 teaches that “Immunohistochemistry protocols and kits are well known in the art and are commercially available.” Thus, the skilled artisan would be motivated to include the Baker et al. antibody/immunohistochemistry methods within the modified Zhang et al. methodology because Baker et al. teaches that these protocols and kits are well-known and commercially available.
The skilled artisan would have a reasonable expectation of success based on the disclosures of Zhang et al. in view of Cho et al., and further in view of Baker 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
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