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
Applicant’s election of the species of MRD and TERT and TP53 in the reply filed on 1/19/2026 s 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)).
Claims 83-102 are pending. Claims 1-82 have been cancelled.
Claims 95-96 and 101-102 are withdrawn as being drawn to a nonelected species.
An action on the merits for claims 83-94 and 97-100 is set forth below.
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.
Claims 83-94 and 97-100 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.
Claims 83-94 and 97-100 are indefinite over the phrase “level of utDNA”, This term is not explicitly defined in the specification. The term typically encompasses “amount” or “fraction”, however, claim 84 indicates that level is equivalent to detection of a mutation. As such this term is unclear as it is not clear the metes and bounds of the phrase.
Claim 91 is indefinite over “calculating a threshold” as it requires multiple subjects, however, the claims only require one subject.
Claim, 92 is indefinite over the phrase “utDNA is at or above 2.3%” or “below 2.3%”. This phrase is unclear as it is not clear what the percentage is measuring. The percentage can encompass a multitude of measurements including fractional and concentration and as such it is not clear the metes and bounds of percent.
Claim 97 is indefinite over “higher risk”. The term “higher risk” in claim 97 a relative term which renders the claim indefinite. The term “higher risk” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In particular as there is no comparison step it is not clear which risks would be considered “higher”.
Claim 98 is indefinite over “reduction in MRD” and “increase in MRD”. The terms in claim 98 a relative term which renders the claim indefinite. The term “higher risk” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In particular as there is no comparison step it is not clear which MRD would be considered a reduction or increase in MRD.
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 therefor, subject to the conditions and requirements of this title.
Claims 90-92 and 97-98 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation without significantly more. The claim(s) recite(s) a judicial exception of correlation of level of utDNA and MRD positive or negative or pCR. This judicial exception is not integrated into a practical application because the claims require steps of determining expression profiles does not provide a step to integrate the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not integrate the judicial exception to steps that are not considered routine and conventional steps.
These judicial exceptions are not integrated into a practical application because the claims only recite the natural correlation and routine and convention steps, wherein the routine and convention steps does not integrate the judicial expectation. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps are considered general and routine knowledge in the prior art as exemplified by the prior (as discussed below).
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, a natural phenomenon.
The correlation of analyzing date and evaluation of radiotherapy is considered a natural correlation. The step of providing determining the level of utDNA in the sample are considered a routine and conventional step as detailed below.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as the steps require only routine and convention steps and does not integrate the judicial exception to a practical application.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No as the claims do not require any elements that integrate the judicial exception.
The steps that are not considered judicial expectations are the steps of determining utDNA level. Melnkova et al. (US Patent Application Publication 2018/0087114 March 29, 2018) teaches providing biological sample from a patient with urinary tract associated cancer comprising urine and detecting utDNA level (para 119). Melnkova et al. teaches that the level of utDNA comprises a mutation in MRD associated genes (para 94).Melnkova et al. teaches a mutation is a non-silent (para 59, 61-67). Melnkova et al. teaches detection after chemotherapy but prior to surgery and correlation of response to chemotherapy (para 36-57). Melnkova et al. teaches detection of mutations in TERT and TP53 (para 60).
These methods are considered generic recitations of general methods of expression determination that do not overcome the rejection.
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 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(s) 83-90, 93-94, 98-99 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Melnkova et al. (US Patent Application Publication 2018/0087114 March 29, 2018)
With regard to claim 83, Melnkova et al. teaches providing biological sample from a patient with urinary tract associated cancer comprising urine and detecting utDNA level (para 119).
With regard to claim 84, Melnkova et al. teaches that the level of utDNA comprises a mutation in MRD associated genes (para 94).
With regard to claim 85, Melnkova et al. teaches a mutation is a non-silent (para 59, 61-67).
With regard to claims 86-87, Melnkova et al. teaches detection after chemotherapy but prior to surgery and correlation of response to chemotherapy (para 36-57).
With regard to claims 88-89, Melnkova et al. teaches detection of mutations in TERT and TP53 (para 60).
With regard to claim 90, Melnkova et al. teaches that mutations of MRD genes are detected (para 57) as such the subject would be positive for the mutation and considered MRD-positive. \
With regard to claim 93, Melnkova et al. teaches that the sample can be urine cfDNA Z(para 68 and 70).
With regard to claim 94, Melnkova et al. teaches kidney, bladder and prostate cancer (para 65).
With regard to claim 98, Melnkova et al. teaches that an increase in utDNA after treatment is associated with development of treatment resistance (para 57).
With regard to claim 99, Melnkova et al. teaches that the subject that does not have a mutation is treated chemotherapy (p. para 119-124) and as such would be consider a bladder sparing treatment as the bladder is not removed.
Claim Rejections - 35 USC § 103
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 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.
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.
Claim(s) 91,. 92, 97 is/are rejected under 35 U.S.C. 103 as being unpatentable over Melnkova et al. (US Patent Application Publication 2018/0087114 March 29, 2018) in view of Arena et al. (US Patent Application 2016/0311908 October 27, 2016).
Melnkova et al. teaches providing biological sample comprising urine and detecting utDNA level (para 119). Melnkova et al. teaches that the level of utDNA comprises a mutation in MRD associated genes (para 94). Melnkova et al. teaches a mutation is a non-silent (para 59, 61-67).Melnkova et al. teaches detection after chemotherapy but prior to surgery and correlation of response to chemotherapy (para 36-57). Melnkova et al. teaches detection of mutations in TERT and TP53 (para 60).
However, Melnkova et al. does not teach these mutation levels are associated with pathologic complete response.
With regard to claims 91 and 97, Arena et al. teaches measuring cfDNA levels of (para 41) to determine pathologic complete response (e.g. risk) (para 96).
With regard to claim 92, as noted in the 35 USC 112b it is not clear the metes and bounds of the measurement of “at or above 2.3%)”. As Arena et al. teaches pathologic complete response based upon cfDNA levels, Arena suggests the measurement of this correlation in patients.
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Melnkova et al. to determine pCR as taught by Arena et al. The ordinary artisan would be motivated to determine a correlation to pCR as pCR provides rather there is any cancer cells in the samples after neoadjuvant therapy. Therefore it would be obvious to perform a determination of a routine measurement to determine if there is correlations with the MRD levels.
Claim(s) 100 is/are rejected under 35 U.S.C. 103 as being unpatentable over Melnkova et al. (US Patent Application Publication 2018/0087114 March 29, 2018) in view of Zimmermann et al. (US Patent Application 2019/0316184 October 17, 2019).
Melnkova et al. teaches providing biological sample comprising urine and detecting utDNA level (para 119). Melnkova et al. teaches that the level of utDNA comprises a mutation in MRD associated genes (para 94). Melnkova et al. teaches a mutation is a non-silent (para 59, 61-67).Melnkova et al. teaches detection after chemotherapy but prior to surgery and correlation of response to chemotherapy (para 36-57). Melnkova et al. teaches detection of mutations in TERT and TP53 (para 60).
However, Melnkova et al. does not teach determining the subject does not have MRD is not administered a radical cystectomy.
With regard to claim 100, Zimmerman et al. teaches a method of measuring MRD based upon measuring TP53 (para 837 and 712). Zimmerman et al. teaches that when there is MRD that radical cystectomy was performed (para 885-898). As such it would be obvious that if there is no indication of MRD a radical cystectomy would not be performed.
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Melnkova et al. to further make treatment decisions including radical cystectomy based upon the presence of MRD. The ordinary artisan would be motivated to determine such assessments in order to provide the least invasive treatment to a patient.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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/KATHERINE D SALMON/ Primary Examiner, Art Unit 1682