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 .
This Office Action is in reply to Applicants’ correspondence of 10/28/2025.
Applicants’ remarks and amendments have been fully and carefully considered
but are not found to be sufficient to put the application in condition for allowance. Any
new grounds of rejection presented in this Office Action are necessitated by Applicants’
amendments. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action.
This Action is made FINAL.
Claim Status
Claims 1, 2, 5, 7, 9, 11, and 12 have been amended.
Claims 15 and 16 remain withdrawn.
Claims 4, 10, and 17-19 have been canceled.
Claims 1-3, 5-9 and 11-14 are currently pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/30/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objection to the Specification
The objection to the disclosure as set forth on page 3 of the Office Action of
05/29/2025 is withdrawn in light of the amendment to the specification provided by
applicant in the reply of 10/28/2025, which is entered.
Withdrawn Rejections
The rejection of claim 9 under 112(b) as being indefinite is withdrawn in view of applicant’s amendments to the claims.
Claim Rejections - 35 USC § 112(b) – Modified – Necessitated by Amendment
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.
Claim 2 stands 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 2 has been amended by applicant to recite “samples that are known to have bladder cancer, known to not have bladder cancer, or known to have bladder cancer and known to not have bladder cancer.” The claim amendment does not provide further clarity on what sample type is being used for the reference values. Applicant could amend the claim to say “samples that are known to have bladder cancer, known to not have bladder cancer, or a combination thereof.”
Therefore, the rejection of Claim 2 set forth under 35 U.S.C. 112 (b) is maintained.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or
composition of matter, or any new and useful improvement thereof, may obtain a patent
therefore, subject to the conditions and requirements of this title.
Claims 1-3, 5-9 and 11-14 stand rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (an abstract idea) without significantly more. The claim(s) recite(s) limitations of comparing cell-free DNA lengths and quantities, calculating values using differences in quantity of DNA, determining classification of cancer, and determining treatment plans. This judicial exception is not integrated into a practical application because and the rationale is described below:
The unpatentability of laws of nature and abstract ideas was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Diamond v. Diehr, 450 U.S. 175, 185 (1981); see also Bilski v. Kappos, 561 U.S._,_(2010) (slip op., at 5). “Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U. S. 63, 67 (1972).
Additionally, the unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010) and in Alice Corp. v. CLS Bank Inti, 134 S. Ct. 2347, 2354 (2014).
The following inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim to a process, machine, manufacture, or composition of matter?
Rejection: Yes, the claims are directed to methods.
Step 2A, prong 1. Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)?
Rejection: Yes, the claims are drawn to concepts that are abstract ideas; they encompass the mental comparison of data and the correlation of data and information to reach a conclusion.
Applicant Argument:
Applicant argues that at least claim 14 cannot be practically performed mentally as a person cannot practically perform claim 1 when “the total amount of DNA fragments at the multiple sizes is greater than 100,000 DNA fragments.”
Response to Argument:
Quantifying the recited amount of DNA fragments mentally may not be ideal, however, an artisan skilled in the art is capable of collecting and analyzing such data using technology that is routine and conventional within the art; further encompassing the mental comparison and correlation of data and information to reach a conclusion.
Step 2A, prong 2. Does the claim recite additional elements that integrate the exception into a
practical application?
Rejection: No, the judicial exceptions to which the claims are directed are not integrated into a practical application because the rejected claims do not require any particular practical steps related to the measuring of DNA or treating of disease that are not considered routine.
Applicant Argument:
Applicant argues that the claims integrate judicial exception into a practical application because the claims improve medicine and biology, particular for diagnostic technology.
Response to Argument:
The examiner acknowledges, though the use of urinalysis technology allows for an improved and safer method of diagnosing for disease, the claims are directed to calculating, quantifying values, determining classification of bladder cancer and treatment plans. The application or use of the claimed invention does not meaningfully limit the claim by going beyond generally linking the use of the judicial exception to a particular technological environment, thus classifying the claims as patent-ineligible subject matter. See MPEP 2106.04 (d)(1).
Step 2B. Does the claim recite additional elements that amount to significantly more than the
judicial exception?
Rejection: No, the claims include practical steps related to the measurement of cell free DNA in urine, sequencing DNA and aligning reads to references and treating cancer, but the broadly recited steps are properly considered routine and conventional and the claims are not significantly more than the judicial exceptions to which they are directed.
Applicant Argument:
Applicant argues that the measuring step is drawn specifically to sizes of urinary cell-free DNA.
Response to Argument:
As previously stated, measuring cell free DNA is regularly found in the art (e.g., Jian et al. pg E1324). Though the claims recite “for each size of a plurality of sizes: measuring an amount of DNA fragments from the urine sample corresponding to the size.” Irrespective of the number and size of urine samples, a quantifying step of measuring DNA fragments is a practical step that is not significantly more than the judicial exception in which it encompasses. Furthermore, the detection of cell-free DNA in urine samples is shown to be routine in the art as demonstrated by Burnham et. al. (Burnham et.al., Urinary cell-free DNA is a versatile analyte for monitoring infections of the urinary tract, Nature Communications, 2018) Burnham teaches the utility of urinary cell-free DNA for monitoring host and pathogen dynamics in bacterial and viral urinary tract infections. Measurements and analysis of fragments were collected from Urine samples for quantification (pg.2, right column).
For these reasons, the rejection of claims 1-3, 5-9 and 11-14 set forth under 35 U.S.C. 101 for being directed to non-statutory subject matter is maintained.
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.
Claims 1-3, 5-9 and 11-14 stand rejected under 35 U.S.C. 103 as being unpatentable over Jiang et. al. (2015; NPL 181 on IDS dated 05/10/2023) in view of Casadio et. al. (2012).
Rejection: Regarding claim 1, Jiang et al teaches a method of analyzing fragments of cell-free DNA from an organism by measuring the amounts of cell-free DNA from plasma corresponding to lengths of fragments, reading on the limitation (e.g., Jiang et al., abstract; Fig. 4) “analyzing a sample including cell-free DNA fragments, the method comprising: for each size of a plurality of sizes: measuring an amount of DNA fragments corresponding to the size” of the instantly rejected claim 1. Jiang et al further teaches calculating values based on parameters of amounts of DNA fragments of different sizes are present in a sample (e.g., Jiang et al., page E1320, left column, para 2-3; right column para 1-2) where the parameter increase with changes in size of DNA fragments (e.g., Jiang et al, abstract), and determining an association with cancer based on the comparison of the sample value against a reference (e.g., Jiang et al., page E1324, left column, para 4; page E1320, right column, para 1-2), reading on the limitation “calculating a first value of a first parameter based on the amounts of DNA fragments at multiple sizes, the first parameter providing a statistical measure of a size profile of DNA fragments in the urine sample, wherein the first parameter increases with increasing size of the DNA fragments; comparing the first value to a reference value; and determining a classification of a cancer based on the comparing” of the instantly rejected claim 1.
Applicant Argument:
Regarding claim 1, applicant has amended to recite the limitation “determining that bladder cancer exists based on the first value being greater than the reference value.” Applicant argues that Jiang et. al. fails to teach independent claim 1 which requires that the first value of the first parameter increases with increasing size of the DNA fragments, in addition to the newly amended limitations. Jiang et. al. teaches that a positive value of ∆S for a particular size indicates a higher abundance of DNA shorter than the particular size.” (Jiang et. al. E1320)
Response to Argument:
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Casadio teaches the method of analyzing cell-free DNA collected from urine to diagnose bladder cancer, associating larger cell-free DNA fragments with bladder cancer when compared to urine samples from patients known to not have bladder cancer. Casadio recites “Median values of UCF DNA integrity were significantly different in the subgroups; the value was significantly (P 0.0001) lower (0.004 ng/ l, range 0–1.883) in healthy individuals, more than 3-fold higher in symptomatic individuals (0.014 ng/ l, range 0–0.864), and about 40-fold higher (0.15 ng/ l, range 0–4.460) in cancer patients (P 0.0001).”, associating an increase in DNA fragment size with increasing parameter and the existence of bladder cancer, teaching the limitations of instant claim 1 (Casadio et. al., title, pg. 1745, left column, par. 4; pg. 1746, right column par.3).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to combine the method of collecting cell-free DNA from urine and the association between cell-free DNA fragment size with that of bladder cancer of Casadio with the method of analyzing a plurality of cell-free DNA fragment size and quantity to associate it to cancer of Jiang. The skilled artisan would have been motivated to use the teachings of Casadio et al of analyzing cell-free DNA from urine for early non-invasive diagnosis of bladder cancer as an alternative to voided cytology. Newly amended dependent claims 2, 5, 7, 9, 11, and 12 do not overcome the previous rejection; the teachings of Casadio still apply. See prior 5/29/2025 Office Action pg. 9
For these reasons, the rejection of claims 1-3, 5-9 and 11-14 set forth under 35 U.S.C. 103 is maintained.
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.
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/A.H.B./Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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