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 .
Election/Restrictions
1. Applicant’s election of the species CD66a as a marker protein present in urinary microvesicles in the reply filed on October 20, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
2. Claims 1-8 are pending and under consideration as drawn to the species CD66a.
Priority
3. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
It is noted that the examiner has established a priority date of August 06, 2021 for claims 1-8 of the instant application because the priority of the instantly claimed invention is based on the prior filed application JP2020-133478 which is written Japanese. The prior filed application has not been translated and the Examiner is unable to determine the information in the document.
If Applicant disagrees with any rejection set forth in this action based on examiner's establishment of a priority date of August 06, 2021 for claims 1-8, then Applicant is invited to submit a proper translation of the priority document and to point to page and line where support can be found establishing an earlier priority date. If Applicant chooses to file a translation, then the translation must be filed together with a statement that the translation of the certified copy is accurate. See 35 U.S.C. 119 (b)(3), 37 C.F.R. 1.55(g)(3)(4), 37 C.F.R. 1.78(d)(7), and MPEP 1895.01.
Drawings
4. The drawings are objected to because Figure 18 is not fully legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
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.
5. Claims 3, 4, 7 and 8 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 3 is drawn to the method according to claim 2, wherein the amount of CD66a, CD66b, CD66c, CGM2, or CD66e present in the microvesicles is observed by calculating a ratio (A/B) of microvesicles (A) expressing CD66a, CD66b, CD66c, CGM2, and CD66e with respect to microvesicles (B) expressing CD10, CD13, and CD26.
The first part of the claim is drawn to the amount of CD66a, CD66b, CD66c, CGM2, or CD66e in the alternative. However, the ratio A/B is drawn to microvesicles (A) expressing CD66a, CD66b, CD66c, CGM2, and CD66e, a combination of all of the markers. Thus, it is unclear if the claim is drawn to determining the amount of CD66a, CD66b, CD66c, CGM2, or CD66e in the alternative or in combination. This renders the claim indefinite.
The claim will be interpreted to include determining the amount of CD66a, CD66b, CD66c, CGM2, or CD66e in the alternative, including in the determination of the ratio A/B, i.e. only one of the recited markers needs to be determined for A.
Claim 4 is drawn to the method according to claim 2, wherein the amount of CD66a, CD66b, CD66c, CGM2, or CD66e present in the microvesicles is observed by calculating a ratio (A/C) of microvesicles (A) expressing CD66a, CD66b, CD66c, CGM2, and CD66e with respect to microvesicles (C) expressing CD10, CD13, CD26, and MUC1.
The first part of the claim is drawn to the amount of CD66a, CD66b, CD66c, CGM2, or CD66e in the alternative. However, the ratio A/C is drawn to microvesicles (A) expressing CD66a, CD66b, CD66c, CGM2, and CD66e, a combination of all of the markers. Thus, it is unclear if the claim is drawn to determining the amount of CD66a, CD66b, CD66c, CGM2, or CD66e in the alternative or in combination. This renders the claim indefinite.
The claim will be interpreted to include determining the amount of CD66a, CD66b, CD66c, CGM2, or CD66e in the alternative, including in the determination of the ratio A/C, i.e. only one of the recited markers needs to be determined for A.
Claim 7 recites “for deciding a therapeutic effect of bladder cancer” on lines 2-3. Given that bladder cancer is a disease, it unclear as to what a therapeutic effect of bladder cancer would be. Thus, the limitation renders the claim indefinite.
Claim 8 recites, “further comprising correlating as indicative of superficial bladder cancer, invasive stage 1 bladder cancer, or invasive stage 2-3 bladder cancer.” The claim does not recite what is being correlated to indicate the various bladder cancer stages. Thus, the claim is unclear and indefinite because what is being correlated is not limited or defined.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
6. Claim(s) 1, 2 and 5-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2010/0196426 A1 (Skog et al. Aug. 5, 2010, IDS), “Skog” in view of Tilki et al. (Euro. Urology 2010 57: 648-654. IDS), “Tilki”.
Skog teaches methods for aiding in the diagnosis or monitoring of a disease or other medical condition in a subject, comprising the steps of: a) isolating a microvesicle fraction from a biological sample from the subject; and b) detecting the presence or absence of a biomarker within the microvesicle fraction, wherein the biomarker is associated with the disease or other medical condition. The methods may further comprise the step or steps of comparing the result of the detection step to a control (e.g., comparing the amount of one or more biomarkers detected in the sample to one or more control levels), wherein the subject is diagnosed as having the disease or other medical condition (e.g., cancer) if there is a measurable difference in the result of the detection step as compared to a control. See ¶¶ 0010.
Skog teaches method for aiding in the evaluation of treatment efficacy in a subject, comprising the steps of: a) isolating a microvesicle fraction from a biological sample from the subject; and b) detecting the presence or absence of a biomarker within the microvesicle fraction, wherein the biomarker is associated with the treatment efficacy for a disease or other medical condition. The method may further comprise the step of providing a series of a biological samples over a period of time from the subject. Additionally, the method may further comprise the step or steps of determining any measurable change in the results of the detection step (e.g., the amount of one or more detected biomarkers) in each of the biological samples from the series to thereby evaluate treatment efficacy for the disease or other medical condition. See ¶¶ 0011.
Skog teaches the biological sample includes urine with urinary microvesicles. See ¶¶ 0012-0013.
Skog teaches detecting protein. See ¶¶ 0017.
Skog teaches diagnosing and monitoring bladder cancer. See ¶¶ 0122 and 0154.
Skog teaches CEACAM1 (CD66a) can be detected for diagnosing and/or monitoring cancer. See Table 12-p. 58-right column and ¶¶ 0134.
Skog does not teach an example of determining the amount of CEACAM1 (CD66a) in urinary microvesicles to diagnose or determine whether or not a patient has bladder cancer.
Tilki teaches CEACAM1 (CD66a) is expressed in normal bladder urothelium and in angiogenically activated endothelial cells, where it exhibits proangiogenic properties. See Abstract-Background and Fig. 1.
Tilki teaches CEACAM1 (CD66a) Western blotting revealed presence of CEACAM1 in the urine of no healthy volunteers, of 76% of noninvasive urothelial carcinoma of the bladder (UCB patients), and of 100% of invasive UCB patients. ELISA analysis confirmed that urinary CEACAM1 levels were significantly higher in UCB patients compared with control subjects. See abstract and Figs. 2-4.
Tilki teaches that higher CEACAM1 (CD66a) levels were associated with the presence of UCB and invasive stage UCB. See Abstract and Table 1.
Tilki teaches that CEACAM1 (CD66a) levels in urine are increased in invasive stages T1-T3 compared control healthy urine samples. See p. 652-left column and Table 1 and See also American Cancer Society (Bladder Cancer Stages, https://www.cancer.org/cancer/types/bladder-cancer/detection-diagnosis-staging/staging.html, downloaded Dec. 3, 2025, p. 1-11) for bladder cancer staging.
Tilki teaches urinary CEACAM1 (CD66a) levels discriminate UCB patients from non-UCB subjects. Tilki teaches, urinary levels of CEACAM1 (CD66a) increased with advancing stage and grade. See abstract and p. 653-Conclusions.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Skog and Tilki to detect increased amounts of CD66a in urinary microvesicles compared to a control to detect bladder, observe progress of bladder cancer treatment, and/or decide a therapeutic effect of a bladder cancer treatment because Skog teaches diagnosis or monitoring of a disease or the evaluation of treatment efficacy by detecting the presence or absence of a biomarker within the microvesicle fraction compared to a control, using CEACAM1 (CD66a) as maker and diagnosing and monitoring bladder cancer and Tilki teaches that higher urinary CEACAM1 (CD66a) levels were associated with the presence of UCB and invasive stage UCB. Thus one would have been motivated to us CEACAM1 (CD66a) as urinary microvesicles marker in the methods of Skog for diagnosing and monitoring bladder cancer treatment because Tilki teaches urinary CEACAM1 (CD66a) levels discriminate UCB patients from non-UCB subjects and urinary levels of CEACAM1 (CD66a) increased with advancing stage and grade.
7. Claim(s) 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over US 2010/0196426 A1 (Skog et al. Aug. 5, 2010, IDS), “Skog” in view of Tilki et al. (Euro. Urology 2010 57: 648-654. IDS), “Tilki” as applied to claims 1, 2 and 5-8 above, and further in view of JP 2019-215342 A (Kang et al. Dec. 19, 2019, IDS), “Kang”.
As noted above, given the indefiniteness of claims 3 and 4, the claim will be interpreted to include determining the amount of CD66a, CD66b, CD66c, CGM2, or CD66e in the alternative, including in the determination of the ratio A/B or A/C, i.e. only one of the recited markers needs to be determined for A, e.g., CD66a.
Skog and Tilki teach as set forth above, but do not teach calculating a ratio (A/B) of microvesicles (A) expressing CD66a with respect to microvesicles (B) expressing CD10, CD13, and CD26 or calculating a ratio (A/C) of microvesicles (A) expressing CD66a with respect to microvesicles (C) expressing CD10, CD13, CD26 and MUC1.
Kang teaches a method for isolating microvesicles from urine to separate them from other components in urine. See Kang-Translation (Appendix), p. 2-6th full paragraph and p. 3-paragraphs 1st -4th paragraphs.
Kang teaches CD10, CD13, CD26 and MUC1 as markers for detecting and isolating microvesicles from urine of a healthy subject. See Kang-Translation, page 4-7th full paragraph to p. 5-1st full paragraph and Examples 1, 2, and 6.
Kang teaches that the method allows easy characterization of urine microvesicles and can be combined with additional surface antigens for clinical applications. See Kang-Translation, 2nd and 3rd paragraphs.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Skog, Tilki and Kang and determine the ratio of microvesicles expressing CD66a with respect to microvesicles (B) expressing CD10, CD13, and CD26 or with microvesicles (C) expressing CD10, CD13, CD26 and MUC1 because Kang teaches that CD10, CD13, CD26 and/or MUC1 can be used to isolate microvesicles from other components normal urine. Thus, one would have be motivated to calculate the ratio of microvesicles expressing CD66a with respect to microvesicles (B) expressing CD10, CD13, and CD26 or with microvesicles (C) expressing CD10, CD13, CD26 and MUC1 to determine the change in level of microvesicles expressing CD66a comparted to total microvesicles isolated for diagnosing and monitoring bladder cancer treatment because Kang teaches that the method allows easy characterization of urine microvesicles and can be combined with additional surface antigens for clinical applications and because Tilki teaches urinary CEACAM1 (CD66a) levels discriminate UCB patients from non-UCB subjects and urinary levels of CEACAM1 (CD66a) increased with advancing stage and grade.
Conclusion
8. No claims allowed.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Janet L Epps-Smith can be reached at 571-272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PETER J REDDIG/ Primary Examiner, Art Unit 1646