DETAILED ACTION
Applicant's response, filed 07/07/2025, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Herein, "the previous Office action" refers to the Final rejection of 03/04/2025. An additional Advisory Action was mailed 06/06/2025.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/07/2025 has been entered.
Claim Examination Status
Claims 1, 9-10, 13, 16-18, and 20-25 are currently pending and under exam herein.
Claims 2-8, 11-12, 14-15, and 19 are cancelled. Claims 14-15 were previously cancelled (10/23/2024) as discussed in the 06/06/2025 Advisory Action.
Claim 25 is newly added.
Claims 1, 9-10, 13, 16-18, and 20-25 are rejected.
Priority
The previously discussed claim for the benefit of priority assigned an effective filing date of claims 1, 9-10, 13, 16-18, and 20-25 were examined for an effective filing date of 07/27/2018.
Withdrawn Rejections/Objections
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn in view of the amendments and Applicant remarks, filed 07/07/2025.
The claim objections in the previous office action are hereby withdrawn, in view of claim amendments.
The rejection under 35 U.S.C. § 101, regarding claims 1, 9-10, 13, 16-18, and 20-25 is hereby withdrawn, in further view of instant application amendments which provide practical integration of judicial exceptions with steatosis treatment administration and followup.
The rejection under 35 U.S.C. § 112(b) for is hereby withdrawn for indefiniteness regarding independent claims 1 and 13, step (c) lack of clear antecedent. The remaining indefinite claim limitations recited in the prior action under 35 U.S.C. § 112(b) are maintained, as they were not addressed by amendment or discussed on their merits, as discussed below.
Upon further consideration, newly applied rejections/objections/portions are necessitated by instant application amendment.
Remarks on Prior Art
As was previously noted, claims 1, 9-10, 13, 16-18, and 20-25 appear free from the prior art as the prior art does not teach nor fairly suggest the functions recited in claims 1, 9-10, 13, 16-18, and 20-25, along with the particular claimed ranges for each of the coefficients for each factor in the functions.
The closest prior art is Poynard (WO 2006/103570 A2; IDS cited). Poynard ‘570 discloses a method for detecting the extent of alcoholic or non-alcoholic steatohepatitis in a patient (abstract). Poynard ‘570 discloses that the method includes using a logistic function that includes 7 biomarkers and age and gender on pg. 6, line 16 to pg. 7, line 30, however, this logistic function does not include the markers for cholesterol and triglyceride and the proposed intervals for the coefficients are different from those set forth in the claimed invention. In addition, other prior art documents that are related to the prediction of NASH or NAFLD but also do not teach nor fairly suggest the particular claimed functions.
The prior art made of record but not relied upon is considered pertinent to applicant's disclosure, as follows:
Shen et al. (Journal of Hepatology 2012, vol. 56, pgs. 1363-1370; previously cited) discloses diagnosis of NAFLD and NASH using biomarkers including CK-18 and FGF21.
Ratziu et al. (Alimentary Pharmacology & Therapeutics 2006, vol. 25, pgs. 207- 218; previously cited) reviews different types of liver pathology tests, including the NASH test. While the NashTest overlaps with the biomarkers utilized, there is no teaching nor suggestion to arrive at the claimed function and coefficient values.
Poynard et al. (BMC Gastroenterology 2006, 6:34, pgs. 1-16; previously cited) discloses the development of the NashTest algorithms. Similar to Ratziu et al., although the NashTest overlaps with the biomarkers utilized, there is no teaching nor suggestion to arrive at the claimed function and coefficient values.
Poynard et al. US Patent Application (16/333,667, PCT/EP2017/073241; previously cited) discloses diagnosing and treating NASH steatohepatitis without liver biopsy and different thresholds, although there are analogous biomarkers, common coefficients (reference claim 32) and functions that include bilirubin.
Specification Objections
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered, for example references of Fedchuk (p2) and Neuschwander (p20).
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.
Claims 1, 9-10, 13, 16-18, and 20-25 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. The dependent claims 9-10, are also rejected because they depend on and/or do not remedy the deficiencies inherited by their parent claims.
Regarding claims 1, 13, 17-18, and 21, the claims recite coefficients a0-a11 as “wherein the function is a0 + a1 x Age (years) + a2 …” and further limited by claim amendments which recite “wherein (a) 4.8 <a0< 5.5, (b) -0.03 <a1< -0.015, (c) 0.9 <a2< 1.2…” without defining steps or criteria for one of ordinary skill in the art to apply the additionally recited numerical ranges for each coefficient and perform their respective mathematical functions [0071-0097].
Regarding claim 9, which is dependent on claim 1, the claim recites “the function” which is indefinite for lack of antecedent basis. Additionally, claim 9 introduces a second function with specific coefficient values without guidance or criteria for one of ordinary skill in the art for use when claim 1 recites an antecedent steatosis function (“a0 + a1 x Age (years) + a2…”) with a a0-a11 group of coefficient ranges. It is indefinite how claim 1 operates with the two recited but different functions.
Regarding claim 10, which is dependent on claims 9 and 1, steps (b) and (c) are indefinite. The claim recites “the end value” and “predetermined values” in “wherein the predetermined value… if the end value is higher or equal to 0.25 and does not have nonalcoholic steatohepatitis (steatosis) if the end value is below 0.25”. There is insufficient antecedent basis for “ the end value” limitation in the claim and is unclear if it refers to claim 1 steps (b) and (c) “comparing the end value to predetermined values…calculated in (a)” or the end results of the function recited in claim 9. Further, “the predetermined value” is indefinite as to whether it is the threshold value for both: claim 9 function and/or only the claim 1 step (a) function determining steatosis.
Regarding claim 13, steps (d) and (e ) recite “determining the presence of liver …” and therefore, lack antecedent basis for identified liver fibrosis/inflammation. This rejection may be overcome with amendments such as, “determining presence of liver fibrosis…inflammation” or the equivalent. Alternatively, step (f) may be placed before steps (d) and (e ), to provide antecedent basis with “diagnosing a liver disease…according to presence of liver fibrosis or presence of liver inflammation…” For compact examination, it is assumed the suggested amendment or an equivalent will be entered.
Regarding claim 16 which depends on claim 13, the claim recites “wherein the presence of liver fibrosis” is determined by…” is indefinite, without a predetermined value or threshold which indicates the presence of liver fibrosis to one of ordinary skill in the art, as is recited for determining the presence of steatosis (claims 1, 9-10, and 23).
Regarding claim 17 which depends on claim 13, the claim recites “wherein the presence of liver inflammation” is determined by the combination of the values of the biological markers by a function…” is indefinite, without a predetermined value or threshold which indicates the presence of liver inflammation to one of ordinary skill in the art, as is recited for determining the presence of steatosis (claims 1, 9-10, and 23).
. Regarding claim 18, which depends from claim 1, the claim recites a second group of coefficients ranges, a0-a11, for the recited logistic regression function without any explanation for one of ordinary skill in the art to guide selection of the antecedent coefficient group recited in claim 1 versus that recited in the dependent claim 18. Further, as amended, both claims 1 and claim 18 now refer to two different ranges for each of a0-a11 (and inherently, two different versions of (i)-(xii)) for the same function in independent claim 1.
Regarding claim 21, which depends from claim 13, the claim recites a second group of coefficients, a0-a11, for the recited logistic regression function without any explanation for one of ordinary skill in the art to guide selection of the antecedent coefficient group recited in claim 13 versus that recited in the dependent claim 21. Further, as amended, both claims 13 and claim 21 now refer to two different ranges for each of a0-a11 for the same function in independent claim 13.
Regarding claim 22, which is dependent on claim 13, the claim is indefinite for lack of antecedent basis with “the function” while introducing a second function with coefficient values without guidance or criteria for one of ordinary skill in the art for use when claim 13 recites an antecedent steatosis function (“a0 + a1 x Age (years) + a2…”) with a0-a11 group of coefficient ranges. It is indefinite how said claim operates with the two recited but different functions.
Regarding claim 23, which is dependent on claims 22 and 13, the term “the end result” in ““wherein the predetermined value… if the end result is higher or equal to 0.25 and does not have nonalcoholic steatohepatitis (steatosis) if the end result is below 0.25” for claim 13 steps (b) and (c) are indefinite. There is insufficient antecedent basis for this limitation in the claim and is unclear if it refers to claim 13 step (b) “end value” as in “end value to predetermined values” or the end results of the function recited in claim 22. Further, “the predetermined value” is indefinite as to whether it is the threshold value for both: claim 22 function and/or the claim 13 step (a) function determining steatosis.
Said claim limitations are indefinite and clarification is requested through clearer claim language.
Remarks pertaining to Arguments regarding 112b
Applicant's arguments (p13-15), filed 07/07/2025, have been fully considered and are not persuasive, as neither claim amendments nor Applicant’s remarks addressed the merits of the 112(b) rejection.
Conclusion
No claims are allowed.
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/VR/
Examiner
Art Unit 1685
/MARY K ZEMAN/Primary Examiner, Art Unit 1686