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 .
Detailed Action
Summary
This is the Final Office Action based on application 17/089448 response filed 10/16/2025.
Claims 4-6, 26-27, 30-42 are pending and have been examined and fully considered.
Claims 1-3, 7-25, 28-29 & 43-44 have been cancelled.
Claim Objections
Claim 4 is objected to because of the following informalities:
In Claim 4, step b) it is claimed--- determining, “the treatment dose.” Everywhere else in the claim it is referred to as “a dose,” and “the dose.” Though it is clear what applicant means by “the treatment dose,” it is best practice to use the same terminology throughout the claim to prevent confusion.
Further, in Claim 4, “in need thereof,” in the preamble is generally understood however this is a somewhat relative term that can read on the scope that any human is “in need thereof,” improvement in mitochondrial function. Therefore, either clarification or deletion of this term might be useful to applicant if they do not intend this scope.
Appropriate correction is required.
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 4-6, 26-27, & 30-42 (and claims dependent therefrom) 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.
With respect to Claim 4, the claimed, “improving,” in the preamble and last two lines of the claim remains unclear. As amended 10/16/2025 “the urolithin A improves mitochondrial function in the human by increasing mitophagy.” However, mitophagy is not measured in the instant claim, and in fact the only measurement that takes place in the claim is measuring of a level of urolithin A. Therefore, if the claimed supposed improvement is not even a positive claim step, but instead is a result of the claimed method, is the preamble really describing what is claimed? This is confusing/unclear. It seems the claim instead is meant to be a method for administering or treating with a specific dose/dosage of urolithin A and of determining the dosage of urolithin A, (or it could be just a method of determining a dose of urolithin A).
Further for Claim 4---though “human in need thereof,” as claimed is clear enough as to who this can include for “improving mitochondrial function,” since a “human in need thereof,” can be interpreted through broadest reasonable interpretation (BRI) as almost any patient the examiner again notes that no mitochondrial function is measured in the instant claim. It is claimed that the dosing of Claim 4, acts to “thereby improving mitochondrial function,” “by increasing mitophagy.” Mitophagy is the cellular process of selectively removing and recycling damaged mitochondria. Therefore, the claimed “improving of mitochondrial function,” seems to be just removing/recycling mitochondria and therefore it is also unclear if “mitochondrial function,” is really “improved,” as claimed since removal of mitochondria does not “improve,” the function of the mitochondria which are removed.
Therefore, the claim overall is not clear.
Claims 5-6, 26-27, & 30-42 are dependent on Claim 4 are also considered unclear as they do not remedy this.
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 non-obviousness.
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.
Claims 4-6, 26-27, & 30-42 are rejected under 35 U.S.C. 103 as being obvious over RINSCH in US 20180256538 in view of ROLTS in US 20180203024.
With respect to Claim 4, RINSCH et al. teach of methods involving oral administration of urolithins according to a specific dosage regime (determination of a treatment dose), resulting in the provision of beneficial health effects, for example improved mitochondrial function and cellular metabolism. The methods are useful for improving the health and wellbeing of subjects, particularly the elderly or frail; and for improving fitness, muscle performance and/or endurance of those engaging in exercise. The methods are also useful in treating or preventing various conditions, e.g. conditions associated with inadequate mitochondrial activity, and/or muscle-related disorders (paragraph 0001).
RINSCH et al. teach of taking a blood sample (paragraph 0338), and of performing urolithin concentration measurements (paragraph 0334), specifically of measuring the concentration of urolithin A glucuronide (paragraph 0455, 0020, 0023). RINSCH et al. further teach of analyzing the sample and of comparison to a standard curve (paragraph 0395). RINSCH et al. further teach of treating the patient/sample with urolithin A (paragraph 0223, 0007), of determining the treatment dose (paragraphs 0032-0033, 0038-0043) and determining if the treatment was effective (See Figures 1-7 & associated description).
RINSCH et al. teach of the compound detected being urolithin A glucuronide (paragraph 0455, 0023), and that steady state levels are 320-820 ng/ml, for example, 380-730 ng/ml, such as 380-640 ng/ml, such as 450-600 ng/ml, such as about 500 ng/ml (paragraphs 0023-0024). These levels are lower than 50,000 ng/ml. Levels lower than 50,0000ng/ml are taught by RINSCH and therefore treating a patient with levels lower than 50,000 ng/ml would be obvious to one of ordinary skill in the art since the range for treatment in RINSCH is included in the ranges claimed (paragraph 0033).
RINSCH et al. further teaches of giving urolithin A doses in healthy elderly subjects after oral administration of a single dose of 250, 500, or 2000 mg (paragraph 0141). It would have been obvious to one of ordinary skill in the art to give a higher dose to subjects to measure lower in urolithin or to whom has other factors which might decrease longevity and lower doses to patients who already measure higher for urolithin to boost wellbeing (paragraph 0194).
RINSCH teaches of measuring the concentration of urolithin A glucuronide (paragraph 0455, 0020, 0023). RINSCH further teaches of dosing to achieve steady state levels of urolithin in an amount of 200-900 ng/ml (paragraphs 0022-0024). This makes obvious it obvious to one of ordinary skill that if levels below 200 ng/ml are measured to dose with an amount that would move the level in a person to this steady state range. RINSCH teaches that a 500 mg does unexpectedly resulted in improved pharmacokinetics (paragraph 0007 Figure 2-7), but that 1000 mg can also be administered (paragraph 0296, 0301, 0461, 0538). Therefore- RINSCH makes it obvious to dose with 500 mg or even higher to move someone who is measuring below 200 ng/ml into the steady state range (paragraph 0022-0024, 0033).
In RINSCH, see Figure 13, which shows that from day 0 to day 7, the level of urolithin measured is between 5 and 5 ng/ml and in paragraph 0457, it shows that the patient is dosed on those days with 500 mg urolithin, exactly as claimed.
Through broadest reasonable interpretation, Figure 13 and paragraph 0457 also show that if the level of urolithin measured is low, lets’ say less than 5ng/ml on days 1-7, 500 mg is dosed to the patient each day following. So- through broadest reasonable interpretation, this reads on the claimed dosing of 1000 or 1500 mg, since multiple days of dosing 500mg adds up to equal this.
RINSCH et al. further teach that urolithins are produced in gut microbiota (paragraph 0158), and that administering the urolithin compound increases mitophagy and autophagy and also of improving mitochondrial function (abstract, paragraph 0025, 0032, 0035, 0038, 0175).
RINSCH also teaches of using the urolithin for treatment increasing mitophagy as is instantly claimed as the improvement in mitochondrial function (abstract).
RINSCH et al teach of measuring in urine (paragraph 0532), but do not teach of using a dried blood spot.
ROLTS et al. is used to remedy this and teach of a method for diagnosis of a disease(abstract), and further of using dried blood spots for the sample (paragraph 0082), and that the concentration of the biomarker is determined from this sample (paragraph 0327). ROLTS et al. also teach of the use of urine as the sample (paragraph 0080).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use the dried blood spot sample of ROLTS in the method of RINCSH since it would be obvious and a person in the art would know how to adjust the analysis dependent on the sample type chosen, including dried blood spots and due to the advantages dried blood spots have for easy storage and transfer (ROLTS, paragraph 0449).
With respect to Claim 5, RINSCH et al. teach of giving urolithin A doses in healthy elderly subjects after oral administration of a single dose of 250, 500, or 2000 mg (paragraph 0141).
RINSCH further teaches of dosing to achieve steady state levels of urolithin in an amount of 200-900 ng/ml (paragraphs 0022-0024). This makes obvious it obvious to one of ordinary skill that if levels below 200 ng/ml are measured to dose with am amount that would move the level in a person to this steady state range. RINSCH teaches that a 500 mg does unexpectedly resulted in improved pharmacokinetics (paragraph 0007 Figure 2-7). Therefore- RINSCH makes it obvious to does with 500 mg or even higher to move someone who is measuring below 200 ng/ml into the steady state range (paragraph 0022-0024, 0033).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to give a higher dose to subjects to measure lower in urolithin or to whom has other factors which might decrease longevity and lower doses to patients who already measure higher for urolithin to boost wellbeing (paragraph 0194).
With respect to Claim 6, RINSCH et al. teach of giving urolithin A doses in healthy elderly subjects after oral administration of a single dose of 250, 500, or 2000 mg (paragraph 0141).
RINSCH further teaches that a 500 mg does unexpectedly resulted in improved pharmacokinetics (paragraph 0007, Figure 2-7), but that 1000 mg can also be administered (paragraph 0296, 0301, 0461, 0538). RINSCH does not call out specifically measuring the level of 10,000-25000 ng/ml. However, RINSCH further teaches that all people will benefit from urolithin supplement including healthy people and all people. So- this includes people who measure at any urolithin A level (paragraph 0194-0195 & 0192-0193). Therefore- RINSCH makes it obvious to does with 500 mg or even higher to anyone measuring at any urolithin level to improve fitness or to supplement exercise regimen in addition to patients suffering from disease (paragraph 0022-0024, 0033), and also making it obvious to administer a lower does if a lower level is detected.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to give a higher dose to subjects to measure lower in urolithin or to whom has other factors which might decrease longevity and lower doses to patients who already measure higher for urolithin to boost wellbeing (paragraph 0194).
With respect to Claims 26, ROLTS et al. teach of the sample being blood or stool and of the sample being a dried blood spot (paragraph 0080, 0082).
With respect to Claim 27, ROLTS teach of the sample being prepared from whole blood (paragraph 0327). ROLTS further teach of the sample being plasma (paragraph 0061). ROLTS even further teach of the sample being serum (paragraph 0061).
With respect to Claim 30, ROLTS teach of the sample being urine (paragraph 0080).
With respect to Claim 31, RINSCH teaches of measuring the concentration of urolithin A glucuronide (paragraph 0455, 0020, 0023). RINSCH further teaches of dosing to achieve steady state levels of urolithin in an amount of 200-900 ng/ml (paragraphs 0022-0024). This makes obvious it obvious to one of ordinary skill before the effective filing date of the instant invention that if levels below 200 ng/ml are measured to dose with an amount that would move the level in a person to this steady state range. RINSCH teaches that a 500 mg does unexpectedly resulted in improved pharmacokinetics (paragraph 0007 Figure 2-7), but that 1000 mg can also be administered (paragraph 0296, 0301, 0461, 0538). Therefore- RINSCH makes it obvious to does with 500 mg or even higher to move someone who is measuring below 200 ng/ml into the steady state range (paragraph 0022-0024, 0033).
With respect to Claim 32, RINSCH teaches of measuring the concentration of urolithin A glucuronide (paragraph 0455, 0020, 0023). RINSCH further teaches of dosing to achieve steady state levels of urolithin in an amount of 200-900 ng/ml (paragraphs 0022-0024). This makes obvious it obvious to one of ordinary skill in the art before the effective filing date of the instant invention that if levels below 200 ng/ml are measured to dose with an amount that would move the level in a person to this steady state range. RINSCH teaches that a 500 mg does unexpectedly resulted in improved pharmacokinetics (paragraph 0007, Figure 2-7), but that 1000 mg can also be administered (paragraph 0296, 0301, 0461, 0538). RINSCH does not call out specifically measuring the level of 10,000-25000 ng/ml. However, RINSCH further teaches that all people will benefit from urolithin supplement including healthy people and all people. So- this includes people who measure at any urolithin A level (paragraph 0194-0195 & 0192-0193). Therefore- RINSCH makes it obvious to does with 500 mg or even higher to anyone measuring at any urolithin level to improve fitness or to supplement exercise regimen in addition to patients suffering from disease (paragraph 0022-0024, 0033).
With respect to Claim 33, RINSCH teaches of measuring the concentration of urolithin A glucuronide (paragraph 0455, 0020, 0023). RINSCH further teaches of dosing to achieve steady state levels of urolithin in an amount of 200-900 ng/ml (paragraphs 0022-0024). This makes obvious it obvious to one of ordinary skill in the art before the effective filing date of the instant invention that if levels below 200 ng/ml are measured to dose with am amount that would move the level in a person to this steady state range. RINSCH teaches that a 500 mg does unexpectedly resulted in improved pharmacokinetics (paragraph 0007 Figure 2-7). Therefore- RINSCH makes it obvious to does with 500 mg or even higher to move someone who is measuring below 200 ng/ml into the steady state range (paragraph 0022-0024, 0033).
With respect to Claim 34, RINSCH teaches of measuring the concentration of urolithin A glucuronide (paragraph 0455, 0020, 0023). RINSCH further teaches of dosing to achieve steady state levels of urolithin in an amount of 200-900 ng/ml (paragraphs 0022-0024). This makes obvious it obvious to one of ordinary skill in the art before the effective filing date of the instant inveniton that if levels below 200 ng/ml are measured to dose with an amount that would move the level in a person to this steady state range. RINSCH teaches that a 500 mg does unexpectedly resulted in improved pharmacokinetics (paragraph 0007, Figure 2-7). RINSCH does not call out specifically measuring the level of 10,000-25000 ng/ml. However, RINSCH further teaches that all people will benefit from urolithin supplement including healthy people and all people. So- this includes people who measure at any urolithin A level (paragraph 0194-0195 & 0192-0193). Therefore- RINSCH makes it obvious to does with 500 mg or even higher to anyone measuring at any urolithin level to improve fitness or to supplement exercise regimen in addition to patients suffering from disease (paragraph 0022-0024, 0033).
With respect to Claim 35, RINSCH teaches of administering 250 mg/day or urolithin A (paragraph 0150).
With respect to Claim 36, RINSCH teaching of administering 500 mg/day or urolithin A (paragraph 007, 0146).
With respect to Claim 37, RINSCH teaches of administering 1000 mg/day (paragraph 0278, 0279).
With respect to Claim 38, RINSCH teaches of administering 2000 mg/day of urolithin A (paragraph 0278-0280). This means that the patient is administered 1500 mg/day since 2000 mg/day is more than 15000 mg/day.
With respect to Claims 39-40, RINSCH et al. further teach that urolithins are found in pomegranates (paragraph 0158) which can be considered a dietary supplement or specialized nutrition through broadest reasonable interpretation, so it is obvious that one could dose for urolithin with pomegranate juice. RINSCH et al. further teach of measuring pre-dosing, and post dosing (paragraphs 0154 & 0155 & 0457).
With respect to Claim 41, RINSCH teaches of the mitochondrial function being associated with aging (paragraph 0209), and of treating/improving mitochondrial functional (paragraph 0212, 0220).
With respect to Claim 42, RINSCH teaches of measuring the levels/collecting samples 24 hours after a dose, determining what the urolithin dose is also at the beginning of the study (paragraph 0457).
Response to Arguments
Applicant's arguments filed 10/16/2025 have been fully considered but they are fully not persuasive.
The 112 rejection is maintained and updated as shown above for claims as amended 10/16/2025.
With respect to the prior art, applicant argues that RINSCH, who is the same inventor as of the instant application does not teach of determining future urolithin A dosing based on previously recorded plasma or urine levels of urolithin A glucuronide.
With respect to this, the examiner disagrees—as shown above the RINSCH prior art actually teaches of measurement of any level of urolithin and then dosing with 250, 500, and at least 1000 mg regardless of level measured. This reads on and in the very least makes obvious to determine further dosing or urolithin A based on current levels of urolithin A.
Applicant argues that the office does not point out any disclosure of the RINSCH prior art which recites specific doses of urolithin A based on specific levels of urolithin A measured in a biological sample. The examiner again disagrees.
Specifically, RINSCH teaches of taking a sample (blood or plasma, paragraph 0334, 0018, 0023) and making multiple measurements and specifically of measuring UA levels at the start of the study, and for example taking two softgel capsules of the UA (capsules are 250 mg each) for each day of 28 days. RINSCH teaches of measuring the steady state levels for 24 hours after a dose (paragraph 0457).
Therefore, RINSCH teaches of measuring levels of UA, that are not 0, and continuing to dose daily with 500mg (total of two capsules of 250 mg, so which also reads on through BRI of dosing twice each day with 250 mg of urolithin A) of Urolithin A. So- this does in fact read, through broadest reasonable interpretation on the “future,” dosing contained in Claims 4 & 43.
Specifically see Figure 13, which shows that from day 0 to day 7, the level of urolithin A measured is between 5 and 5 ng/ml and in paragraph 0457, it shows that the patient is dosed on those days with 500 mg urolithin, exactly as claimed.
Through broadest reasonable interpretation, Figure 13 and paragraph 0457 also show that if the level of urolithin measured is low, let’s say less than 5ng/ml on days 1-7, 500 mg is dosed to the patient each day following. So- through broadest reasonable interpretation, this reads on the claimed dosing of 1000 or 1500 mg, since multiple days of dosing 500mg adds up to equal this. In addition, since each softgel capsule is 250 mg, anytime 500 mg is dosed, it also reads on the claimed dosing with 250 mg.
The examiner further notes that due to the many “if,” clauses in the instant independent claims the examiner notes that the claims are left open to only one dosing situation to be taught for the prior art to read on the instant claims. The claimed method dose not require all dosing instances claimed to actually occur for the instant prior art to read on the instant claims---- however it is the examiner’s position that the RINSCH prior art used still makes all of the “if,” limitations obvious and reads on them as shown above, even though they are not actually required in the claims.
Applicant further argues that RINSCH does not disclose the relationship of any level of urolithin A glucuronide with specific does of urolithin. The examiner see what applicant is saying, but maintains that due to the broad language, the prior art RINSCH can be interpreted as shown above, in a specific way that reads on the instant very broad claim language. Again—due to the “if,” statements for all of the dosage options, to read on the claim language, the prior art only needs to teach one. The RINSCH prior art does more than this as shown above.
Therefore, all claims remain rejected.
Conclusion
THIS ACTION IS MADE FINAL. 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 REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758