DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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 and Arguments
2. Claims 1-4, 6, 9, 10 and 16-24 are pending.
Claims 16-24, drawn to a non-elected inventions are withdrawn from examination.
Claims 5, 7, 8 and 11-15 have been cancelled.
Claims 1, 9 and 10 have been amended.
Claims 1-4, 6, 9 and 10 are examined on the merits with species (cancer): breast cancer.
3. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on July 16, 2021 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. However, Foreign Patent Document, #1 cites the incorrect WO number, 20014015229. After a cursory search and investigation, it is the Examiner’s perspective the correct number is WO 2014/015229 A1 (published 23 January 2014).
Applicant is put on notice all IDS information should be correct and complete. In the future such errors may result in the IDS not being considered by the Examiner.
Withdrawn Objections
Claim Objections
5. The objection of claims 1 and 8 has been withdrawn because:
claim 1, line 11 no longer recites “in” after “precancerous lesion”; and claim 8 has been cancelled.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 112
6. The rejection of claims 1-4, 6, 9 and 10 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of amendments submitted June 30, 2025. Claims 5, 7, 8 and 11-15 have been cancelled.
7. Claim 8 has been cancelled, hence the rejection noting insufficient antecedent basis is withdrawn.
Claim Rejections - 35 USC § 101
8. The claimed invention (claims 1-4, 6, 9 and 10) is no longer directed to a judicial exception (i.e. a law of nature, a natural phenomenon, or abstract idea) without significantly more, see Amendments to the Claims and Remarks, both submitted June 3, 2025. Claims 5, 7, 8 and 11-15 have been cancelled.
Claim Rejections - 35 USC § 102
9. The rejection of claim(s) 1-4 and 6 under 35 U.S.C. 102(a)(1) as being anticipated by DeFilippis et al. (Cancer Discovery 826-839, September 2012/ IDS Non-Patent Literature Documents reference #1 submitted July 16, 2021) and by DeFilippis et al. Supplementary Figures, pages 1-8; and Supplementary Figure and Table Legends, pages 1-27 (Cancer Discovery, pages 1-8, September 2012) is withdrawn in light of the amendment to claim 1, see Amendments to the Claims and Remarks, both submitted June 3, 2025. Claims 5, 7, 8 and 11-15 have been cancelled.
Claim Rejections - 35 USC § 103
10. The rejection of claim(s) 1-4 and 6 under 35 U.S.C. 103 as being unpatentable over DeFilippis et al. (Cancer Discovery 826-839, September 2012/ IDS Non-Patent Literature Documents reference #1 submitted July 16, 2021), and further in view of Finak et al. (Nature Medicine 14(5): 518-527, published online 27 April 2008/ IDS reference #4 submitted July 16, 2021) is withidrawn. Claims 5, 7, 8 and 11 have been cancelled.
Maintained Objections
Claim Objections
11. The objection of claim 6 is not withdrawn because of the following informality:
a. claim 6, line 2 recites “cd36”, while the other examined claims recite “CD36”. Applicants should cite the acronym that is consistent with the abbreviation noted in the claims and Specification.
Correction is required.
Maintained Grounds of Rejection
Claim Rejections - 35 USC § 103
12. 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.
13. 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.
14. The rejection of claim(s) 1-4, 6, 9 and 10 under 35 U.S.C. 103 as being unpatentable over DeFilippis et al. (Cancer Discovery 826-839, September 2012/ IDS Non-Patent Literature Documents reference #1 submitted July 16, 2021), and further in view Merriam-Webster’s Dictionary of Law, 1 page (1996) and Clarke et al., US 2007/0099209 (published May 3, 2007) is maintained and made. Claims 5, 7, 8 and 11-15 have been cancelled.
Applicant does not reference the instant rejection in the Remarks submitted June 3, 2025, see entire document and particularly page 6, VI. Accordingly, the rejection is maintained and made.
DeFilippis teaches discerning histology between “desmoplastic tissue and histologically normal adjacent tissue from a patient with invasive ductal carcinoma.”, see Figure 1 on page 828. CD36 expression is stained for and observed at different levels within “paraffin sections [between] tumor and normal adjacent tissue from 8 ER-positive tumors, 6 HER2-positive tumors, and 6 triple negative tumors”, see Figure 6B on page 834. Histological sections were listed from a list of women including those with ductal carcinoma in situ (DCIS), see Supplemental Figure and Table Legends, page 24 and Supp. Figure S8.
“In all tumor subtypes, CD36 expression was strikingly absent in the tumor field compared with the normal adjacent tissue (Fig. 6B). Cell-by-cell quantitation of CD36 staining (Supplementary Fig. S1) revealed that CD36 expression was reduced 14.7-fold (P < 10−8) in tumor tissue compared with normal adjacent tissue (Supplementary Fig. S7). This was due to a decrease in both the percentage of CD36-positive cells and the intensity of CD36 staining per cell (Supplementary Fig. S6).”, see page 832, 2nd column, 1st full paragraph (para.).
“Staining of serial sections for endothelial and macrophage markers CD31 and CD68, respectively, revealed that endothelial cells and macrophages were still present within the field of tumor tissue, albeit with repressed CD36 expression (Supplementary Fig. S7).”, see para. bridging pages 832 and 835.
“Tissue sections were stained for CD36, imaged in the tumor, normal adjacent, and normal distal fields (Fig. 7A–C, left panels) and quantified for CD36 expression on a cell-by-cell basis (Supplementary Fig. S1). In accordance with the results reported above, CD36 expression was reduced in the tumor compared with normal adjacent and normal distal tissues in all 3 women (4.7-fold to 113-fold and 6.8-fold to 159-fold, respectively, P < 10−8; Fig. 7A and B). Consistent with the hypothesis above, we observed in 2 of 3 cases that the normal adjacent tissue exhibited CD36 repression compared with its matched normal distal tissue (1.4-fold, P < 10−8; Fig. 7A and B).”, see page 835, 2nd column.
“An important and novel finding of our study is that repression of CD36 is observed in both stroma associated with a malignant lesion and in breast tissue with high mammographic density in the absence of malignancy.”, see page 836, 2nd column, 2nd sentence. Absent evidence to the contrary, the stromal tissue adjacent to the precancerous lesion comprises tissue within 0.5 to 2.0 mm of the lesion border, see page 827, 2nd column, 1st full paragraph (para.); page 832, 2nd column, CD36 Expression is Decreased in Multiple Cell…segment.
DeFilippis does not teach the risk of invasive cancer progression is determined by comparing the measured abundance of CD36-expressing vasculature to a threshold value, wherein a measured abundance of CD36-expressing vasculature below, at least 50% lower than the threshold value (a median or mean abundance value of CD36-expressing vasculature observed in healthy stromal tissue) is indicative of elevated risk of progression to invasive cancer and treatment should be administered.
However, Merriam-Webster teaches a threshold is a minimum requirement for further action or a determination, see entire page.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize CD36 expression to arrive at threshold values indicative of an elevated risk of progression to invasive breast cancer between 50% and 60% at 2 mm2 and 8 mm2 because it is art known a threshold value is a minimum requirement for further action or point at which a determination is made or identified and this said transmembrane receptor affects clinical outcomes, see DeFilippis, 2nd column (col.), CD36…segment and page 836, Clinical…segment.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings in all references, particularly DeFilippis that clinical and pathological assessments reading on different classes or subtypes of breast tumors are indicative of the risks of progressive breast cancer. These risks can be easily determined based on the valuation of an observed prognostic indicator, CD36 and its measures and level of expression exceeding or meeting predetermined thresholds.
Furthermore, Clarke teaches establishing cancer gene signatures useful for the diagnosis, characterization, prognosis and treatment are useful for methods for treating, characterizing and diagnosing cancer, see Abstract.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize determined thresholds and the assessment of candidate breast cancer biomarker(s) to assess risk for an invasive event and commence with treatment for the breast cancer including mastectomy, hormonal therapy, chemotherapy and/or radiation therapy based upon the characterization of the cancer, see page 1, sections 0005-0008; page 6, section 0060; page 72, section 0352; section 0331 bridging pages 70 and 71; page 88, section 0454; and Example 8 beginning on page 89.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings in all references that clinical and pathological observations such as the level of CD36 expression is a risk factor associated with mammographic density and tumor stroma, see DeFilippis abstract. “Levels of CD36 and extent of mammographic density are both modifiable factors that provide potential for [therapeutic] intervention” and definitive classification of different classes or subtypes of breast tumors should aid and provide information guiding those skilled in the art to select the proper treatment to be administered based on these observations, see all references in their entirety and in particular, DeFilippis, abtract on page 826, paragraph bridging pages 836 and 837; and Clarke.
Conclusion
15. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
- Puchkova et al., Breast density as a risk factor of development of ductal carcinoma in situ. Clin. Experiment Surg. Petrovsky J. 7(2): 53-59, 2019.
16. 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.
17. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached on 8AM-8PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
October 7, 2025
/Alana Harris Dent/Primary Examiner, Art Unit 1643