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 .
Response to Amendments
This office action is in reply to Applicant’s response of 16 April 2026. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance.
The Declaration Under 37 C.F.R. § 1.130(a) has been fully and carefully considered.
Note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
This action is made FINAL.
Withdrawn Objections and Rejections
The objections to the specification in the Office Action mailed 20 January 2026 are withdrawn in view of Applicant’s amendments to the specification filed 16 April 2026.
All rejections of claim 2 are withdrawn in view of claim 2 being canceled, rejections that recited claim 2 are modified as necessitated by the cancelation of claim 2.
The rejections of claims 9 and 11 under 35 U.S.C. 112(b) as being indefinite are withdrawn in view of Applicant’s amendments to the claims filed 16 April 2026.
The rejection of claims 1, 3-6, and 12 under 35 U.S.C. 102(a)(1) as being anticipated by Ahn et al. (Non-Patent Literature Document 1 in IDS filed 17 May 2023)(“5P Exploratory biomarker analysis from neoadjuvant atezolizumab, pertuzumab, trastuzumab plus docetaxel (NEO-PATH) in HER2+ early breast cancer”, Abstract only, European Society for Medical Oncology, Vol. 33, Supplement 3, S125-126 (1 May 2022)), herein Ahn, as evidenced by FoundationOne CDx Technical Information (Wayback Machine snapshot dated 6 March 2022)(downloaded from https://web.archive.org/web/20220306112918/https://assets.ctfassets.net/w98cd481qyp0/41rJj28gFwtxCwHQxopaEb/fba378cd309082f09570f32fc16b5d01/FoundationOne_CDx_Label_Technical_Info.pdf), herein FoundationOne, is withdrawn. In view of the Declaration Under 37 C.F.R. § 1.130(a) filed 16 April 2026, the subject matter disclosed in Ahn is attributed to Inventors of instant application. The publication date of Ahn is greater than one year before the filing date of instant application, but within the 102(b)(1) grace period of one year before the applications KR 10-2022-0086734 (filed 14 July 2022) and KR 10-2023-0046214 (filed 7 April 2023) to which the instant application claims priority. Certified copies of both KR applications have been received. In view of the machine translations of KR 10-2022-0086734 and KR 10-2023-0046214, provided with this Office Action:
Of the claims rejected over Ahn, KR 10-2022-0086734 provides support for instant claims 1, 3, and 12, but does not provide support for instant claims 4-6 because it does not teach an agent for detecting a RNA expression level of the RAD21 gene, as recited in claim 4 (and claim 5 via its dependency on claim 4), and does not teach an agent selected from the group consisting of primers, probes, and antisense nucleotides, which bind to RNA of the RAD21 gene, see KR 10-2022-0086734 machine translation [0007-0024]. Priority for claims 7-11 was not assessed because they were not rejected over Ahn.
Of the claims rejected over Ahn, KR 10-2023-0046214 provides support for instant claims 1, 3-6, and 12, see KR 10-2023-0046214 machine translation [0008-0027]. Priority for claims 7-11 was not assessed because they were not rejected over Ahn.
Therefore, the effective filing date of claims 1, 3, and 12 is 14 July 2022 and the effective filing date of claims 4-6 is 7 April 2023. In view of the Declaration Under 37 C.F.R. § 1.130(a) filed 16 April 2026, Ahn’s disclosure of the subject matter of claims 1, 3-6, and 12 on 1 May 2022 is therefore excepted under 35 U.S.C. 102(b)(1) and the rejection of claims 1, 3-6, and 12 under 35 U.S.C. 102(a)(1) as being anticipated by Ahn as evidenced by FoundationOne is withdrawn.
Information Disclosure Statement
The information disclosure statement (IDS) filed 28 April 2026 is considered, initialed, and attached hereto.
Claim Status
Claims 1 and 3-21 are pending. Claims 1, 3, 9, and 11-12 are currently amended.
Claim 2 is canceled.
Claims 13-21 are withdrawn.
Claims 1 and 3-12 are under examination.
Claim Interpretation
Modified as Necessitated by Amendment
In claim 1, the body of the claim fully and intrinsically sets forth all of the limitations of the claimed invention: a “composition containing an agent for detecting RAD21 gene”. The preamble states an intended use, “for predicting prognosis of treatment of HER2-positive early breast cancer”, but this intended use does not provide any distinct definition of any of the claimed composition’s limitations. The clause “wherein […] immunotherapeutic anticancer agent” in lines 4-6 of claim 1 further limits the intended use but does not provide any distinct definition of any of the claimed composition’s limitations. Claim 3 further limits the intended use, but the limitations to the intended use do not provide any distinct definition of any of the claimed composition’s limitations. Therefore, the intended use of claims 1 and 3-12 is not interpreted as limiting the composition claimed in claims 1 and 3-12.
Claim Rejections - 35 USC § 112(b) – Indefiniteness
New – Necessitated by Amedment
Claim 9 is 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.
Claim 9 recites the limitation "the agent for measuring an expression level of PDL1 gene or protein" in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112(d) - Dependent Form
Maintained – Modified as Necessitated by Amendment
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 3 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. Claim 3 claims a composition, which is described in claim 1 on which it depends. Claim 3 fails to further limit the composition because it only limits the intended use, but the further limits on the intended use fail to further limit the structure of the composition (as described in the claim interpretation section above). Therefore, claim 3 is in improper dependent form. 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.
Response to Arguments
Applicant's arguments filed 16 April 2026 have been fully considered and are persuasive in part. On page 9 of Applicant’s arguments, Applicant responds that claim 2 is canceled and claim 3 is amended. Regarding claim 2, Applicant’s argument is persuasive. The rejection under 35 U.S.C. 112(d) of claim 2 is withdrawn because claim 2 is canceled. Regarding claim 3, Applicant’s argument is not persuasive. Claim 1, on which claim 3 depends, recites an intended use “for predicting prognosis of treatment of HER2-positive early breast cancer” and limits that use in the clause “wherein […] immunotherapeutic anticancer agent” on lines 4-6 of claim 1. As discussed in the Claim Interpretation section above, this intended use does not structurally limit the claimed composition (also see MPEP §2111.02(II) regarding preamble statements reciting purpose or intended use). The intended use therefore holds no patentable weight. As claim 3 only recites a further limitation of the intended use and this further limitation does not lead to any structural limitation of the claimed composition, the limitation has no patentable weight and the scope of claims 1 and 3 is identical. Applicant does not provide any arguments that the limitations indicated as a non-structurally limiting intended use identified in the Office Action of 20 January 2026 provide a structural limitation. Therefore, claim 3 fails to further limit the claim it depends on and is rejected under 35 U.S.C. 112(d) as being in improper dependent form.
Claim Rejections - 35 USC § 102
Maintained – Modified as Necessitated by Amendment
Claims 1, 4, and 6-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Illumina Data Sheet Pub. No. 470-2008-005 ("HumanHT-12 v3 Expression BeadChip", 2008), herein Illumina 1, as evidenced by Illumina HumanHT-12 v3.0 Manifest File (TXT Format)(24 May 2013)(downloaded from https://support.illumina.com/downloads/humanht-12_v3_product_files.html), herein Illumina 2.
Regarding claims 1, 4, and 6, Illumina 1 teaches a composition (“each array on the HumanHT-12 Expression BeadChip” [page 1, paragraph labeled “Content”]) that contains agents for detecting the RNA expression level of multiple genes (“targets more than 25,000 annotated genes with more than 48,000 probes” [page 1, paragraph labeled “Content”]). However, Illumina 1 does not teach that the specific targets of the agents include the RAD21 gene. Illumina 2 teaches the specific probe sequences of the HumanHT-12 Expression BeadChip taught by Illumina 1 as well as the targets of those probes, providing evidence that the composition of Illumina 1 contains an antisense nucleotide probe that binds to RNA of the RAD21 gene ([Illumina 2 page 12 lines 10 and 12]). Therefore, Illumina 1 teaches a composition containing an agent for detecting the RNA expression level of the RAD21 gene wherein the agent is an antisense nucleotide probe that binds to RNA of the RAD21 gene, which would be capable of fulfilling the intended use as a composition for predicting prognosis of treatment of HER2-positive breast cancer. The composition disclosed in Illumina 1 containing an agent for detecting the RNA expression level of the RAD21 would be capable of fulfilling the intended use as a composition for predicting prognosis of treatment of HER2-positive early breast cancer patients wherein the treatment is a neoadjuvant chemotherapy comprising a HER2-targeted therapeutic agent, a cytotoxic anticancer agent, and an immunotherapeutic anticancer agent.
Regarding claim 3, the composition disclosed in Illumina 1 containing an agent for detecting the RNA expression level of the RAD21 would be capable of fulfilling the intended use as a composition for predicting prognosis of treatment of HER2-positive early breast cancer patients wherein the treatment is a neoadjuvant chemotherapy that comprises docetaxel, paclitaxel, or nanoparticle albumin-bound (nab) paclitaxel; trastuzumab; pertuzumab; and atezolizumab, nivolumab, or pembrolizumab.
Regarding claims 7 and 9, Illumina 1 teaches a composition that contains an agent for detecting the RAD21 gene and contains an agent for measuring an expression level of HER2 gene (HER2 is a synonym of ERBB2 [evidenced by Illumina 2, page 4 line 11]) that is an antisense nucleotide probe that binds to the HER2 gene. Notably, claim 9 requires the limitation that the agent for measuring an expression level of HER2 gene or protein binds to the HER2 gene or protein or PDL1 gene or protein, which would not be met by an agent that binds only to the HER2 transcript but not the HER2 gene or protein. The HER2 probe of the HumanHT-12 Expression BeadChip taught by Illumina 1, listed on page 4 line 11 of Illumina 2, is able to bind to the HER2 gene as confirmed by the BLASTn alignment below.
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BLASTn alignment: Query is the full sequence of the HER2 probe.
Regarding claim 8, Illumina 1 teaches a composition that contains an agent for detecting the RAD21 gene and contains an agent for measuring an expression level of PDL1 gene (PDL1 is a synonym of CD274 [evidenced by Illumina 2, page 10 line 28]).
Regarding claims 10 and 11, Illumina 1 teaches a composition that contains an agent for detecting the RAD21 gene and contains an agent for measuring an RNA expression level of ANKRD50 gene that is a probe that binds to the RNA sequence of ANKRD50 ([evidenced by Illumina 2, page 9 line 35]), an agent for measuring an RNA expression level of COX6C gene that is a probe that binds to the RNA sequence of COX6C ([evidenced by Illumina 2, page 11 line 26]), an agent for measuring an RNA expression level of DERL1 gene that is a probe that binds to the RNA sequence of DERL1 ([evidenced by Illumina 2, page 8 line 41]), an agent for measuring an RNA expression level of FLNB gene that is a probe that binds to the RNA sequence of FLNB ([evidenced by Illumina 2, page 7 line 35]), an agent for measuring an RNA expression level of GPRC5A gene that is a probe that binds to the RNA sequence of GPRC5A ([evidenced by Illumina 2, page 13 line 25]), an agent for measuring an RNA expression level of RNF139 gene that is a probe that binds to the RNA sequence of RNF139 ([evidenced by Illumina 2, page 14 line 14]), an agent for measuring an RNA expression level of SAMD8 gene that is a probe that binds to the RNA sequence of SAMD8 ([evidenced by Illumina 2, page 2 line 15]), an agent for measuring an RNA expression level of SERPINE1 gene that is a probe that binds to the RNA sequence of SERPINE1 ([evidenced by Illumina 2, page 6 line 17]), an agent for measuring an RNA expression level of SQLE gene that is a probe that binds to the RNA sequence of SQLE ([evidenced by Illumina 2, page 3 line 3]), and an agent for measuring an RNA expression level of TTC39A gene that is a probe that binds to the RNA sequence of TTC39A ([evidenced by Illumina 2, page 5 line 44]).
Regarding claim 12, Illumina 1 teaches a kit (the HumanHT-12 Expression BeadChip [page 1, paragraph labeled “Content”]) that comprises the composition (each array of the HumanHT-12 Expression BeadChip [page 1, paragraph labeled “Content”]) of claim 1, as discussed regarding claim 1 above.
Maintained – Modified as Necessitated by Amendment
Claims 1 and 3-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al. (Non-Patent Literature Document 2 in IDS filed 13 October 2023)("Enhanced RAD21 cohesin expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancers", Breast Cancer Res 13, R9 (2011)), herein Xu, as evidenced by Theisen (“Microarray-based Comparative Genomic Hybridization (aCGH)”, Nature Education 1(1):45 (2008)).
Regarding claims 1, 4, and 5, Xu teach the use of a composition (an array CGH [page 5 paragraph 2]) containing an agent for detecting a DNA mutation of the RAD21 gene wherein the mutation is a copy number variation (“we examined RAD21 […] gene copy number in an integrated array CGH” [page 5 paragraph 2]). Xu also teaches the intended use of the composition for predicting prognosis of treatment of HER2-positive breast cancer (“RAD21 expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancers” [page 1 abstract]) and the disclosed composition would be capable of fulfilling the intended use as a composition for predicting prognosis of treatment of HER2-positive early breast cancer wherein the treatment is a neoadjuvant chemotherapy that comprises a HER2-targeted therapeutic agent, a cytotoxic anticancer agent, and an immunotherapeutic anticancer agent.
Regarding claim 3, the composition disclosed in Xu containing an agent for detecting a copy number variation of the RAD21 gene would be capable of fulfilling the intended use as a composition for predicting prognosis of treatment of HER2-positive early breast cancer patients wherein the treatment is a neoadjuvant chemotherapy that comprises administering docetaxel, paclitaxel, or nanoparticle albumin-bound (nab) paclitaxel; trastuzumab; pertuzumab; and atezolizumab, nivolumab, or pembrolizumab.
Regarding claim 6, Xu teaches claim 1 as described above. However, Xu does not explicitly teach that the agent is a primer, probe, and/or antisense oligonucleotide and that the agent binds to the DNA or RNA of the RAD21 gene. Theisen provides evidence that an array CGH that targets a genomic area of interest, such as a gene, necessarily contains a probe that binds to the DNA of that gene (“the basic methodology for aCGH analysis is consistent […] two genomic DNAs, test and reference, are then mixed together and applied to a microarray […] thus, when applied to the slide, they attempt to hybridize with the array single-strand probes” and “probes vary in size from oligonucleotides manufactured to represent areas of interest (25-85 base pairs)” [paragraphs 4-5]. Therefore, Xu teaches a composition containing an agent for detecting the RAD21 gene wherein the agent is a probe that binds to DNA of the RAD21 gene.
Maintained – Modified as Necessitated by Amendment
Claims 1 and 3-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhu et al. ("Suppression of RAD21 Induces Senescence of MDA-MB-231 Human Breast Cancer Cells Through RB1 Pathway Activation Via c-Myc Downregulation", J. Cell. Biochem. 117: 1359-1369 (2015)), herein Zhu.
Regarding claim 1, Zhu teaches a composition containing an agent for detecting RAD21 gene by detecting RAD21 protein expression (“anti-RAD21”; Zhu, page 2, paragraph 7; Zhu, Figure 1A), which would be capable of fulfilling the intended use as a composition for predicting prognosis of treatment of HER2-positive early breast cancer wherein the treatment is neoadjuvant chemotherapy comprising a HER2-targeted therapeutic agent, a cytotoxic anticancer agent, and an immunotherapeutic anticancer agent.
Regarding claim 3, the composition disclosed in Zhu containing an agent for detecting expression of the RAD21 gene would be capable of fulfilling the intended use as a composition for predicting prognosis of treatment of HER2-positive early breast cancer patients wherein the treatment is a neoadjuvant chemotherapy that comprises administering docetaxel, paclitaxel, or nanoparticle albumin-bound (nab) paclitaxel; trastuzumab; pertuzumab; and atezolizumab, nivolumab, or pembrolizumab.
Regarding claim 4, Zhu teaches that the agent for detecting RAD21 is one for detecting an RNA expression level of the RAD21 gene indirectly by detecting RAD21 protein expression and showing that the detection is reduced when the RNA expression level is reduced using siRNAs that target the RAD21 gene (Zhu, Figure 1A; Zhu, page 3, paragraph 6).
Response to Arguments
Applicant's arguments filed 16 April 2026 regarding the rejections under 35 U.S.C. 102 of claims 1, 4, and 6-12 as being anticipated by Illumina 1 as evidenced by Illumina 2, claims 1-6 as being anticipated by Xu as evidenced by Theisen, and claims 1-4 as anticipated by Zhu have been fully considered but they are not persuasive. Applicant maintains that none of the cited references of these rejections disclose HER2-positive early breast cancer treated with neoadjuvant chemotherapy including a HER2-targeted therapeutic agent, a cytotoxic anticancer agent, and an immunotherapeutic anticancer agent. Applicant argues that since a reference must disclose all the features of a claimed invention for an anticipation rejection under §102 and these references do not disclose this specific cancer with this specific treatment, these references fail to anticipate claim 1. Applicant is correct insofar as it is true that these references to not disclose this specific cancer with this specific treatment. However, Examiner holds that these recited features do not limit the claimed composition and therefore are not required to be recited by a reference for the reference to anticipate the claimed composition.
MPEP §2111.02(II) states: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”.
MPEP §2111.04(I) states: “Claim scope is not limited […] by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are: […] (B) "wherein" clauses” […] The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case”.
Considering these portions of the MPEP, the recitation in the preamble “for predicting prognosis of treatment of HER2-positive early breast cancer” is a recitation of an intended use that does not structurally limit the claimed composition containing an agent for detecting RAD21 gene. The “wherein” clause in claim 1 only limits the intended use and does not provide any structural limitation on the claimed composition. See also the discussion of intended use in the Claim Interpretation section above. Because these features of the claim do not structurally limit the claimed composition, they are not limitations holding patentable weight and are not required to be taught by references in order to anticipate claim 1. Therefore, to anticipate claim 1, a reference merely needs to teach a composition containing an agent for detecting RAD21 gene. Since the references in the above rejections under 35 U.S.C. 102 teach a composition containing an agent for detecting RAD21 gene, these rejections are maintained.
Applicant also argues that Illumina 2 (referred to as Illumina ‘Manifest’ in Applicant’s response) should not anticipate the specifically defined invention because of the possibility that the claimed invention might accidentally be arrived at from Illumina 2 and includes a citation from the Federal Circuit regarding accidental reduction to practice and anticipation. As noted in the arguments above, the intended use and limitations to the intended use recited in the claims do not limit the claimed composition. Therefore, the fact that Illumina 2 does not appreciate the disclosed composition containing an agent for detecting RAD21 gene as being useful for the recited intended use is irrelevant because the recited intended use is not limiting. As far as recognition of limiting features of the claimed invention goes, Illumina 2 does appreciate that the disclosed antisense nucleotide is an agent for detecting RAD21 gene because it teaches that the probe sequence is for targeting the RAD21 gene. Therefore, Illumina 2 is not an accidental or unappreciated reduction to practice and the rejection is maintained.
Conclusion
Claims 1 and 3-12 are rejected. Claim 2 is canceled. Claims 13-21 are withdrawn.
Applicant's amendment necessitated the new ground 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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/JEFFREY BELLAH/Examiner, Art Unit 1683
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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