FINAL ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is responsive to the Amendments and Response filed 06 March 2026. Claims 1-2, 6, 9, and 13-14 have been amended and claims 15-17 have been canceled. All prior rejections of claims 15-17 are moot in view of the cancelation of those claims. Claims 3-4 and 18-21 remain withdrawn, and claims 1-2 and 5-14 remain under consideration. Applicant’s amendments and arguments have been thoroughly reviewed, and have overcome the following objections/rejection set forth in the prior Office action:
The objection to claim 9, in view of Applicant’s corrective amendment;
The rejections under 35 USC 112(b) in view of Applicant’s clarifying amendments;
The rejections of claims under 35 USC 102 and 35 USC 103 in view of Applicant’s amendment of claims 1 and 2 to delete the recitation of the B2M gene (such that this elected gene is no longer encompassed by the language of the claims under consideration); and
The nonstatutory double patenting rejection over US Patent No. 11,579,140, in view of Applicant’s amendments canceling claims 15-17 (i.e., those claims directed to treating subjects), such that all claims under consideration in the present application now correspond to Group II of the restriction/election requirement issued in the parent application (16/545,032) from which the ‘140 patent issued.
Claims 1-2 and 5-14 remain rejected for the reasons given below, which include new grounds of rejection necessitated by Applicant’s amendment. Any rejections and/or objections not reiterated in this action have been withdrawn. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Applicant's election with traverse of the species of the gene combination previously recited in claim 2 (CIITA; NLRC5; EPSTI1; UBE2L6; B2M; and TAP1) in the reply filed on 05 November 2025 is again acknowledged. It is noted that each of claims 1 and 2 have been amended to delete the B2M gene from the claims, such that the remaining genes now set forth in claim 2 are CIITA, NLRC5, EPSTI1, UBE2L6, and TAP1.
Claims 3-4 and 18-21 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 05 November 2025.
Comment Regarding Applicant’s Request for Clarification
Although it is reiterated that the prior art rejections set forth in the prior Office action have been withdrawn (as indicated above), the Beane et al reference (Clinical Cancer Research 23(17):5091 [Sept 2017; online May 2017]; cited in IDS) is again relied upon below (in a different rejection). Applicant’s comment regarding this reference on page 12 of the Reply of 06 March 2026 is noted, and it is confirmed that the rejection referred to (and again refers to) the 2017 reference cited above (which was provided by Applicant in an IDS, as noted). The other (2019) Beane et al reference (Nature Communications doi.org/10.1038/s41457-019-09834-2, 13 pages [23 April 2019]; previously cited) was cited by the examiner in the prior PTO-892 of 13 January 2026 because it was referenced by the examiner in paragraph 21 of the corresponding Office action mailed 13 January 2026.
Claim Rejections - 35 USC § 102
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.
THE FOLLOWING ARE NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claim(s) 1-2, 5, 7-8, and 10-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Whitney (WO 2013/1163568 A2 [31 Oct 2013]; cited herein).
It is noted that this rejection is necessitated by Applicant’s amendment of the claims to delete the recitation of “B2M” (a gene of the originally elected species). The claims continue to require “at least one module 9 gene”, with the species under consideration now requiring selection from the group of CIITA, NLRC5, EPSTI1, UBE2L6, and TAP1.
Whitney discloses “methods of determining the likelihood that a subject has lung cancer based on the expression of informative-genes” (see entire reference, particularly the Abstract and the Summary at pages 1-10). Whitney teach methods comprising measuring expression levels in samples, particularly of “certain informative-genes” (including in “apparently histologically normal cells”), which genes may be or include CIITA; see again the Summary at pages 1-10 (including the discussion of obtaining samples and measuring expression levels therein at page 1 bridging to page 2, page 3 bridging to page 4, page 6, page 8 [lines 19-31], page 9 [lines 1-17], and the disclosure of CIITA at page 2, line 20); see also the discussion of samples at page 8 lines 19-27, page 12, lines 1-9, and page 15, line 28-page 16, line 10; the discussion and exemplification of various methods for measuring gene expression levels at page 8 lines 29-31; page 14 lines 7-28; and in Examples 1-2; and the disclosure of CIITA as a preferred “informative-gene” at page 13, line 21; page 34 [gene number 46 in Table 7]; page 39 [Table 8]; page 40 [Table 9]; and see all claims, particularly dependent claims 21, 40, and 48). Whitney thus discloses methods meeting all requirements of claims 1-2 as directed to the elected species of “at least one module 9 gene” that is or that includes CIITA, and anticipate claims 1-2.
With further regard to dependent claims 5-7, Whitney teaches measuring expression levels of “informative-genes” in “a biological sample obtained from a subject during a routine cell or tissue sampling procedure”, where the sample “comprises histologically normal cells”, as well as the testing of “cytologically normal appearing cells collected from the bronchi of a subject”; Whitney also states that the “sampling of histologically normal cells (e.g., cells of the bronchus) is advantageous because tissues containing such cells are generally readily available” (see page 1 bridging to page 2); see also page 8 lines 19-24; page 12 lines 1-9 (noting in particular the teaching of the testing of samples in the airway “that are remote from malignant lung tissue”); and page 15 line 28-page 16, line 10 (noting in particular the teaching that a sample may be “free of detectable cancer cells, e.g., as determined by standard histological or cytological methods”). Whitney thus teaches samples meeting the requirements of claims 5 and 7.
Regarding dependent 8, Whitney teaches preferred samples including nasal and bronchial epithelial samples, as well as samples obtained from bronchial brushings and biopsies (see page 8 lines 19-27; page 12 lines 1-9; page 15, line 28-page 16, line 10).
Regarding claims 10-12, Whitney disclose the practice of their methods on cancer-free subjects (see, e.g., Example 1 at page 26, lines 26-28) and subjects that have a “cancer-free personal history” (see, e.g., page 12, lines 18-19) as well as subjects who are smokers/former smokers (see, e.g., page 12, line 17).
Regarding claims 13-14, Whitney disclose preferred embodiments in which the CIITA gene is included in a preferred group of 36 genes (see Table 9), which method comprises measurement of expression levels of this gene group (as well as several control genes) (see Example 2 at pages 39-41); this meets the requirements of claims 13-14 regarding “no more than” 1000/200 genes other than the module 9 gene being measured.
Whitney thus anticipates all of claims 1-2, 5, 7-8, and 10-14.
Claim Rejections - 35 USC § 103
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 ARE NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claim(s) 6 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Whitney (WO 2013/1163568 A2 [31 Oct 2013]; cited herein) in view of Beane et al (Clinical Cancer Research 23(17):5091 [Sept 2017; online May 2017]; cited in IDS).
It is noted that this rejection is necessitated by Applicant’s amendment of the claims to delete the recitation of “B2M” (a gene of the originally elected species). The claims continue to require “at least one module 9 gene”, with the species under consideration now requiring selection from the group of CIITA, NLRC5, EPSTI1, UBE2L6, and TAP1.
Whitney discloses “methods of determining the likelihood that a subject has lung cancer based on the expression of informative-genes” (see entire reference, particularly the Abstract and the Summary at pages 1-10). Whitney teach methods comprising measuring expression levels in samples, particularly of “certain informative-genes” (including in “apparently histologically normal cells”), which genes may be or include CIITA; see again the Summary at pages 1-10 (including the discussion of obtaining samples and measuring expression levels therein at page 1 bridging to page 2, page 3 bridging to page 4, page 6, page 8 [lines 19-31], page 9 [lines 1-17], and the disclosure of CIITA at page 2, line 20); see also the discussion of samples at page 8 lines 19-27, page 12, lines 1-9, and page 15, line 28-page 16, line 10; the discussion and exemplification of various methods for measuring gene expression levels at page 8 lines 29-31; page 14 lines 7-28; and in Examples 1-2; and the disclosure of CIITA as a preferred “informative-gene” at page 13, line 21; page 34 [gene number 46 in Table 7]; page 39 [Table 8]; page 40 [Table 9]; and see all claims, particularly dependent claims 21, 40, and 48). Whitney thus discloses methods meeting all requirements of independent claim 1 as directed to the elected species of “at least one module 9 gene” that is or that includes CIITA. Further, regarding dependent claim 5 (from which claim 6 depends), Whitney teaches measuring expression levels of “informative-genes” in “a biological sample obtained from a subject during a routine cell or tissue sampling procedure”, where the sample “comprises histologically normal cells”, as well as the testing of “cytologically normal appearing cells collected from the bronchi of a subject”; Whitney also states that the “sampling of histologically normal cells (e.g., cells of the bronchus) is advantageous because tissues containing such cells are generally readily available” (see page 1 bridging to page 2); see also page 8 lines 19-24; page 12 lines 1-9 (noting in particular the teaching of the testing of samples in the airway “that are remote from malignant lung tissue”); and page 15 line 28-page 16, line 10 (noting in particular the teaching that a sample may be “free of detectable cancer cells, e.g., as determined by standard histological or cytological methods”). Whitney thus teaches samples meeting the requirements of claim 5; however, Whitney do not disclose such a sample that further comprises “bronchial premalignant lesion cells” (as set forth in dependent claim 6). With regard to claim 9, it is noted that Whitney do teach that their methods may be performed on samples from subjects that have “been identified as having a suspicious lesion in the respiratory tract and therefore referred for bronchoscopy to evaluate the lesion” (page 3, lines 30-32), and Whitney also teach the testing of bronchial samples (e.g., bronchial brushings and biopsies) (see page 8 lines 19-27; page 12 lines 1-9; page 15, line 28-page 16, line 10). However, Whitney do not provide the specific teaching of a subject “having bronchial premalignant lesions”, as required by the claim.
Beane et al disclose procedures for testing gene expression levels in “normal appearing bronchial mucosa” from smokers both with and without premalignant lesions (PMLs), and teach that many significant differences in gene expression were identified in subjects with PMLs as compared to those without (see entire reference, particularly the Abstract and page 5092, left column, “Subject population used to derive gene signature and biomarker”); such a subject type clearly meets the requirements of claim 9, and a “normal appearing” sample comprising bronchial premalignant lesion cells meets the requirements of claim 6. It is also noted that Beane et al disclose obtaining their samples via bronchial brushing (see page 5092, left column, as well as page 5093, right column), and teach the successful determination of gene expression levels therein. Beane et al further teach that they identified altered expression in their samples of “genes differentially expressed between lung tumor tissue (primarily squamous) and normal lung tissue in three different” established datasets, stating that their results “support the concept that early events in lung carcinogenesis can be observed throughout the respiratory tract, even in cells that appear normal” (page 5095, left column), and also teach that bronchial premalignant lesions “are precursors of lung squamous cell carcinoma and are a risk factor for developing lung cancer at the lesion site or elsewhere in the lung” (page 5092, left column, see gray box). Beane et al also suggest further testing and study of such gene expression biomarkers (page 5097, right column, first full paragraph).
In view of the teachings of Whitney and Beane et al, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have measured the expression of the CIITA gene (as taught by Whitney) in sample types from subject types taught by Beane et al, and thereby to have performed methods meeting the requirements of claims 6 and 9. Both references teach methods comprising determining gene expression levels in bronchial cells of normal appearance and that such methods may aid in early detection of lung cancer, with Whitney teaching the importance of the specific gene CIITA, and Beane et al teaching that the particular samples and subjects as set forth in claims 6 and 9 respectively are relevant targets for such testing. Thus, an ordinary artisan would have been motivated to have so modified the methods of Whitney simply for the benefit of evaluating gene expression of CIITA in the preferred, relevant sample and subject types taught by Beane et al, and more broadly for the benefit of better characterizing any disease present (in particular lung cancer) in such samples/subjects. Additionally, given the detailed guidance provided by both Whitney and Beane et al, an ordinary artisan would have had a reasonable expectation of success in so modifying the methods of Whitney.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DIANA B JOHANNSEN whose telephone number is (571)272-0744. The examiner can normally be reached Monday-Friday, 7:30 am-3:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682
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