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 .
Information Disclosure Statement
The information disclosure statement (IDS) filed 17 May 2023 and 13 October 2023 are considered, initialed, and attached hereto.
Election/Restrictions
Applicant’s election without traverse of Invention I (claims 1-12) drawn to a composition for predicting prognosis of treatment of HER2-positive breast cancer and a kit comprising the composition in the reply filed on filed 05 December 2025 is acknowledged.
Claims 13-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05 December 2025.
Claim Status
Claims 1-21 are pending.
Claims 1-12 are under examination as claims 13-21 are withdrawn from consideration as laid forth above.
Specification
The use of the terms Roche, HiSeq, Illumina, Applied Biosystems, QIAamp, Qiagen, FoundationOne, CDx, RNeasy, Promega, Bioanalyzer, Agilent, and TruSeq which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
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 breast cancer”, but this intended use does not provide any distinct definition of any of the claimed composition’s limitations. Claims 2 and 3 further limit 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 1-12 is not interpreted as limiting the composition claimed in claims 1-12.
Claim Rejections - 35 USC § 112(b)
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 9 and 11 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.
Claim 9 recites the limitation "the agent" in line 1. There is insufficient antecedent basis for this limitation in the claim because it is unclear whether “the agent” refers to “an agent for detecting RAD21 gene” (claim 1 lines 2-3) or “an agent for measuring an expression level of HER2 gene or protein” (claim 7 lines 1-2). For the purpose of examination, “the agent” is being interpreted as referring to the “agent for measuring an expression level of HER2 gene or protein” (claim 7, line 2).
Claim 9 recites the limitation "the [...] PDL1 gene" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the agent" in line 1. There is insufficient antecedent basis for this limitation in the claim because it is unclear whether “the agent” refers to “an agent for detecting RAD21 gene” (claim 1 lines 2-3) or “an agent for measuring an RNA expression level of at least one gene selected from the group consisting of ANKRD50, COX6C, DERL1, FLNB, GPRC5A, RNF139, SAMD8, SERPINE1, SQLE, and TTC39A genes” (claim 10 lines 1-4). For the purpose of examination, “the agent” is being interpreted as referring to the “agent for measuring an RNA expression level of […] genes” (claim 10, lines 2-4).
Claim 11 recites the limitation "the RNA sequence" in line 2. There is insufficient antecedent basis for this limitation in the claim. For the purpose of examination, “the RNA sequence” is being interpreted as referring to the RNA sequence of the gene that the agent detects the RNA expression level of.
Claim Rejections - 35 USC § 112(d)
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.
Claims 2 and 3 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 2 and 3 claim a composition, which is described in claim 1 on which they depend (claim 3 depending on claim 1 via its dependency on claim 2). Claims 2 and 3 fail to further limit the composition because they only limit 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, claims 2 and 3 are 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 1-6 and 12 are rejected 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.
Regarding claims 1-6 and 12, Ahn teaches using a kit (the FoundationOne CDx test; Ahn, Methods) containing a first composition containing an agent for detecting RAD21 gene which is a primer, probe, or antisense nucleotide that binds to DNA (“DNA will undergo […] hybridization-based capture of all coding exons” of the genes in Table 2; FoundationOne, page 4, paragraph 6) of RAD21 (FoundationOne, Table 2, row 16, column 9) and detects DNA mutations in the RAD21 gene including single nucleotide mutation, deletion, substitution, insertion, and copy number variation (“designed to detect […] base substitutions, indels, copy number alterations”; FoundationOne, page 4, paragraph 6). Ahn also teaches the use of the composition for detecting the RAD21 gene in predicting prognosis of treatment of HER2-positive early breast cancer patients to whom neoadjuvant therapy of atezolizumab, docetaxel, trastuzumab, and pertuzumab is applicable (“neoadjuvant atezolizumab plus docetaxel, trastuzumab and pertuzumab therapy showed favorably efficacy and safety profiles in HER2-positive early breast cancer (EBC) in NEO-PATH […] we evaluated potential genomic biomarkers in NEO-PATH”; Ahn, Background; “pre-treatment RAD21 amplification […] [was] more frequently detected in non-pCR group (n=23) compared to pCR group”, Ahn, Results).
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.
Regarding claims 2 and 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 to whom is applicable a neoadjuvant chemotherapy that comprises administering 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.
Claims 1-6 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 breast cancer.
Regarding claims 2 and 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 to whom is applicable 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.
Claims 1-4 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 breast cancer.
Regarding claims 2 and 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 to whom is applicable 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).
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jeffrey Lawrence Bellah whose telephone number is (571)272-1024. The examiner can normally be reached M-Th, 7:30-5 ET.
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/JEFFREY BELLAH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683