DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application is being examined under the pre-AIA first to invent provisions.
2. Claims 58-71 are pending.
Claim 58, drawn to a non-elected invention is withdrawn from examination.
Claims 59-71 have been amended.
Claims 59-71 are examined on the merits.
Withdrawn Objections
Claim Objections
3. Claims 59 and 71 are no longer objected to because no longer recites an acronym for matrix metalloproteinase 9, see Amendments to the Claims submitted November 19, 2025.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 112
4. The rejection of claims 59-71 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 set forth in the first action on the merits (FAOM) mailed May 19, 2025 in segment 7, part b. on page 4 has been withdrawn in light of Applicant’s Amendments to the Claims submitted November 19, 2025.
Claim Rejections - 35 USC § 102
5. The rejection of claim(s) 59-61 and 64-68 under pre-AIA 35 U.S.C. 102(b) as being anticipated by Attallah et al. (International Journal of Cancer Research 2(1): 50-56, 2006/ IDS Non-Patent Literature Document (NPL) reference #2 on sheet 4 submitted January 16, 2024) is withdrawn in light of the amendment to claim 59, see Amendment to the Claims submitted November 19, 2025.
6. The rejection of claim(s) 59-61 and 64-71 under pre-AIA 35 U.S.C. 102(b) as being anticipated by Meso Scale Discovery (MSD®) Applications publication (6 pages, published 2007/ IDS Non-Patent Literature (NPL) reference #16 on sheet 6 submitted January 16, 2024) is withdrawn in light of the amendment to claim 59, see Amendment to the Claims submitted November 19, 2025.
Claim Rejections - 35 USC § 103
7. The rejection of claims 59-68 and 71 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Attallah et al. (International Journal of Cancer Research 2(1): 50-56, 2006/ IDS Non-Patent Literature (NPL) reference #2 on sheet 4 submitted January 16, 2024), and further in view of Tannapfel et al. (J. Pathol. 201: 238-249, published online 26 August 2003/ IDS NPL reference #14 on sheet 5 submitted January 16, 2024) and Ando et al. (European J. Gastroenterology Hepatology 15: 641-648, 2003/ IDS NPL reference #1 submitted January 16, 2024) is withdrawn in light of the amendment to claim 59, see Amendment to the Claims submitted November 19, 2025.
8. The rejection of claims 59-71 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Meso Scale Discovery (MSD®) Applications publication (6 pages, published 2007/ IDS Non-Patent Literature (NPL) reference #16 on sheet 6 submitted January 16, 2024), and further in view of Ando et al. (European J. Gastroenterology Hepatology 15: 641-648, 2003/ IDS NPL reference #1 submitted January 16, 2024) is withdrawn in light of the amendment to claim 59, see Amendment to the Claims submitted November 19, 2025.
New Objections
Claim Objections
9. Claims 59 and 69 are objected to because of the following informality: claim 59 recites both, CA 19.9 (line 4) and CD 19-9 (line 11); and claim 69 cites CA 19-9 (line 2). The Specification cites CA 19-9 at least 34 times, while cites CA 19.9 only twice on page 30. Applicant is advised to select one citation for clarity and consistency.
Correction is required.
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
10. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
11. Claims 59-71 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. THIS IS A NEW MATTER REJECTION. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant has amended claim 59 to recite step “(c) determining from the comparing step the presence or absence of cirrhosis in said patient, wherein cirrhosis is present if the levels of at least two biomarkers in the measured set meet or exceed the normalized median difference score for the at least two biomarkers, wherein the levels of said biomarkers in the test sample are measured using an immunoassay”, see page 3 of the Amendments to the Claims submitted November 19, 2025, page 3.
There seems to be no support for the comparative analysis between at least two biomarkers and the normalized median difference score for the at least two biomarkers, wherein the measured set must meet or exceed the normalized median difference score. The Specification cites “[t]he at least two markers can be measured in two independent assays conducted on one or more patient samples or the measurements can be conducted in a single multiplexed assay.”, on page 6, lines 19-23. However, this citation, nor any other reviewed in the Specification denote specific differences between two test biomarker samples and the normalized median difference score for the corresponding at least two biomarkers. Applicant should delete the new matter or point out where in the Specification support can be found for the stated quantifiable difference in step (c) to arrive at the diagnosis of whether the patient has cirrhosis, as well as disease progression of cirrhosis, or diagnosis of additional non-cancerous liver disease(s).
12. 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.
13. Claims 59-71 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.
a. Newly amended claims 59-71 read on comparing the measured level of each biomarker in a set to a normalized median difference score for each biomarker in the set, wherein the normalized median difference score for AFP is >0.5, the normalized median difference score for CA 125 is > 1, the normalized median difference score for CA 19-9 is >0.5 ng/mL, the normalized median difference score for CEA is >0.1 to determine whether the patient has cirrhosis or not, as well as determining disease progression of cirrhosis and differentiating between cirrhosis and non-cancerous liver diseases.
Applicant asserts “the claims are amended based on the tabulated data in the specification as applicable to cirrhosis” and “now provides quantifiable differences between cirrhosis patients vs. normal”, see Remarks submitted November 19, 2025, pages 5 and 6.
These assertions and pages within the specification have been carefully reviewed and considered, but fail to persuade.
Newly amended step (c) states if at least two biomarkers in the measured set using an immunoassay meet or exceed the normalized median difference score for the at least two biomarkers there is a positive diagnosis of cirrhosis and a therapeutic agent is administered.
However, it is not clear if determining progression of cirrhosis and differentiating between cirrhosis and non-cancerous liver diseases are based upon the same measures.
Moreover, the noted score for CA 19-9 has a unit accompanying the number 0.5, yet the other biomarkers, AFP, CA 125 and CEA do not. Example 2 and Table 4 on page 29 do not have units. Table 6, on the other hand does recite a units for four of the biomarkers, see page 30. Therein, the unit cited for CA 19-9 is U/ml, however in claims it is ng/mL. It seems the numbers set forth in Table 5 are scores and it is not clear how these numbers coincide with the numbers cited in step (b) of newly amended claim 59. Hence, the claims are vague and indefinite, as well as the metes and bounds cannot be determined.
Claim Rejections - 35 USC § 101
14. 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.
15. The claimed invention (claims 59-71) continues to be directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract) without significantly more.
Applicant argues “as amended, which now include additional elements including an administration step amount to significantly more than the judicial exception. The claims are amended in accordance with the holding in In re Vanda and the 2019 Guidelines. As amended, the claims provide a particularized administration of a therapeutic agent only when a specific patient is determined to have cirrhosis.”, see Remarks submitted November 19, 2025, page 7, 1st paragraph (para.).
Applicant’s arguments have been carefully considered, but fail to persuade.
As the claims are written currently, the breath of treatment is expansive. In the instant case, the "natural principle" does not apply the law of nature with the broad recitation “a therapeutic agent”, which can read on an exhaustive list of compounds, agents and modalities. The claim(s) does/do not include additional elements that are sufficient
to amount to significantly more than the judicial exception because of the highly generic “administering a therapeutic agent” step does not integrate the exception in a practical application or amount to significantly more than the exception because it is at best equivalent of merely adding the words “apply it” to the claim.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the dispensation of a random treatment is insignificant because it does not limit the type of therapy that is applicable to the patient population. The breadth of the term, “therapeutic agent” is broad, thus
any treatment modality can be administered. This random therapy is not an additional element or a combination of additional elements in the claim to apply, rely on, or use the natural correlation/natural phenomenon in a manner that imposes a meaningful limit on the judicial exception. The judicial exception has not been applied or used to affect a particular treatment for cancer.
Moreover, the claims cite conditional language, wherein if the levels of at least two measured biomarkers meet or exceed the normalized median difference score of the said two markers, a generic therapeutic agent may be administered if the said condition is met, a positive determination of cirrhosis. However, there are no steps if the at least two biomarkers are lower than the normalized median difference score. It is not clear to one of ordinary skill in the art how to proceed if the condition is not met. There is no clear path recited, which the skilled artisan should execute if at least two biomarkers in the measured set do not meet or exceed the normalized median difference score for the at least two biomarkers.
Accordingly, the rejection is maintained.
The claim(s) 59-71 recite(s) a method for detecting cirrhosis in a patient comprising
(a) receiving a measurement of a set of biomarkers in a test sample from said patient, wherein the plurality of biomarkers is selected from AFP, CEA, CA 125, CA19-9;
(b) comparing the measured level of each biomarker in the set to a normalized median difference score for each biomarker in the set, wherein the normalized median difference score for AFP is >0.5, the normalized median difference score for CEA is >0.1, the normalized median difference score for CA 125 is >1, the normalized median difference score for CA 19-9 is 0.5 ng/mL; and
(c) determining from the comparing step the presence or absence of cirrhosis in said patient, wherein cirrhosis is present if the levels of at least two biomarkers in the measured set meet or exceed the normalized median difference score for the at least two biomarkers, wherein the levels of said biomarkers in the test sample are measured using an immunoassay; and
(d) administering a therapeutic agent to the patient if the determination is positive for cirrhosis. Furthermore, the dependent claims further read on determining disease progression of cirrhosis, as well as differentiating between cirrhosis from liver diseases and from non-cancerous liver diseases based upon imaging the liver and differences in the measurement of a level of a set of biomarkers.
This judicial exception is not integrated into a practical application because gathering information and making a diagnosis based on gathered information required to use the correlation do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
The analysis as set forth in the 2019 Guidance is as follows:
Step 1: Yes, claims are drawn to a method which is one of the four statutory categories, a process.
Step 2A, prong 1: Yes, the claims recite/describe/set forth a judicial exception. Claims 59-71 describe the relationship between a set of biomarkers, AFP, CA 19-9, CA 125 and CEA and a measured level of each biomarker in a normalized median difference score for each biomarker in the set and the comparison is indicative of whether or not the patient has cirrhosis, liver disease, non-cancerous liver disease and progression of cirrhosis. And if the determination is positive for cirrhosis a general therapeutic agent is administered.
Step 2A, prong 2: No, the judicial exception is not integrated into a practical application. The claims do not rely on or use the exception here. Once a plurality of biomarkers has been measured via an immunoassay and compared to the normalized median difference score for at least two biomarkers and the test level of the two biomarkers meet or exceed the normalized median difference score, therapeutic agent is administered. The comparison and determination steps are mental steps, observing the differences in the comparison of the set of levels of between the test sample and control sample and utilizing this information to determining the liver disease and the status of the disease. After the said assessments, there are no additional steps. There are no additional elements or combination of additional elements to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Step 2B: No, there is no inventive concept present in the clams. The steps of analyzing, measuring and comparing levels biomarkers is established by well understood, routine conventional methods and arriving at a therapeutic treatment are regarded as pre-solution activity, i.e. data gathering necessary to perform the correlation. The following claims and steps inform one of ordinary skilled in the art that differences between the measured level of a set of biomarkers in a test sample and control sample allows one of ordinary skill in the art to arrive upon a clinical diagnosis of cirrhosis, liver disease and/or non-cancerous liver disease, as well as prognosis of the malady.
The claim(s) does/do not include, nor recite additional elements that are sufficient to amount to significantly more than the judicial exception. Accordingly, these claims are not be eligible under step 2A or step 2B.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because assaying for a candidate cancer biomarkers and comparing them between the test sample and control sample does not add significantly more and is not an inventive concept. Because methods for making such determinations were well known in the art, these steps simply tell researchers to engage in well-understood, routine, conventional activity previously engaged in by scientists in the field. Such activities are normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such law. Detection of candidate disease biomarkers and comparison between those measured in a test sample and standard/control/reference sample have been observed by applicant but not engineered by applicant. The claims do not add significantly more to the natural phenomenon because the claims do not require for example, a novel reagent, novel apparatus, or incorporate a novel treatment based on the correlation.
A claim that focuses on use of a natural principle must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966. Recited elements such as “receiving”, “comparing” and “determining” based on the natural principle impose no meaningful limit on the performance of the claimed invention. As set forth the claims do not impose meaningful limits on the performance of the claimed invention. Likewise, as well as equations and formulas based on the natural principle impose no meaningful limit on the performance of the claimed invention.
Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas). Further, the active method steps are conventional and routine in the art for the reasons stated above and the claims do not amount to significantly more than the recited natural principle. The claims do not "practically apply" the natural principle; rather, the claims "simply inform" the natural principle to one performing routine active method steps and do not amount to significantly more than the natural principle itself. Thus, the technology used by the instant claims is well-known in the art and does not contribute significantly more to the judicial exception. See the 2019 Revised Patent Subject Matter Eligibility Guidance and Federal Register
https://www.federalregister.gov/documents/2019/10/18/2019-22782/october-2019-patent-eligibility-guidance-update; and FDsys.gov.
Claim Rejections - 35 USC § 103
16. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
17. Claims 59-71 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Attallah et al. (International Journal of Cancer Research 2(1): 50-56, 2006/ IDS Non-Patent Literature (NPL) reference #2 on sheet 4 submitted January 16, 2024), and further in view of over Meso Scale Discovery (MSD®) Applications publication (6 pages, published 2007/ IDS Non-Patent Literature (NPL) reference #16 on sheet 6 submitted January 16, 2024), Tannapfel et al. (J. Pathol. 201: 238-249, published online 26 August 2003/ IDS NPL reference #14 on sheet 5 submitted January 16, 2024) and Ando et al. (European J. Gastroenterology Hepatology 15: 641-648, 2003/ IDS NPL reference #1 submitted January 16, 2024). Attalah teaches a method of assaying carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and -fetoprotein (AFP) in the sera of healthy individuals and individuals with hepatocellular carcinoma and cirrhosis, see Abstract on page 50; and page 51, lines 7-10, Patients… and Serum…segments. Given method steps (a) and (b) within claim 59, cirrhosis as well as progression of cirrhosis is determined. Furthermore, based upon the measures and comparison of the level of plurality of biomarkers between the test sample and control sample, differentiation of liver diseases (cirrhosis, liver diseases and non-cancerous liver diseases) and disease progression of cirrhosis is determined.
All individuals were assayed for the said biomarkers, see page 51, Patients...section; and page 52, Table 1. If the measured level of the serum biomarkers was higher than the cut-off values it was considered positive for disease, see page 51, Serum...section; and page 52, Determination…segment and Table 1. Absent evidence to the contrary, the biomarkers are measured in a multiplexed assay and a single assay chamber, see page 51, Serum…section. Based upon the measures and comparison of the level of at least two biomarkers between the test sample and control sample, differentiation of liver diseases (cirrhosis, liver diseases and non-cancerous liver diseases) and disease progression of cirrhosis is determined.
Attallah does not teach the claimed method, wherein additional biomarker, cancer antigen 125 (CA 125) is measured and the patient is subjected to an imaging method to evaluate size, shape and position of the liver. Attallah also does not teach the diagnosed liver disease is hepatitis.
However, The MSD® publication teaches serum and plasma samples from healthy/normal population and test population can be measured and compared for a level of a plurality of biomarkers between a test sample using the assay protocols disclosed on page 1; and pages 3 and 4. A multiplexed immunoassay panel with a plurality of assay wells comprising cancer antigen 125 (CA 125), as well as AFP, CEA, CA 19-9, cKit, E-cadherin, epidermal growth factor receptor (EGFR), erythroblastic leukemia viral oncogene homolog 2 (erbB2), MMP9 and osteopontin (OPN), see pages 1-4. The publication teaches an electrochemiluminescence-based multiplexed immunoassay panel is able to simultaneously measure the said biomarkers in a 96-well format, see page 1.
Tannapfel teaches assaying and comparing protein levels of additional candidate biomarkers for liver diseases utilizing hepatocellular carcinoma and non-neoplastic liver tissues, see Abstract on page 238; and Table 2 on page 241.
Moreover, Ando teaches imaging studies of the liver (including a patient with hepatitis B virus), as well as measuring the level of several liver disease biomarkers, see Methods on page 641; and page 642, Determination…and Diagnostic process…segments. These studies include ultrasound, computed tomography (CT), angiography, magnetic resonance imaging (MRI), CT-angiography and ultrasound-angiography, see page 642, Diagnostic process…section.
It would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to establish more than one method of evaluating HCC with a combination of techniques, such as measuring additional candidate liver diseases biomarkers and imaging analyses. It would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to assay a multitude of potential liver diseases biomarkers and image the liver via an imaging technique to further yield definitive and discriminate results indicative of distinct liver diseases, as well as progression of liver diseases, see all three documents in their entireties. Ando also notes periodic ultrasound provides good information regarding stage of liver disease, see page 647, last paragraph.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings in all references that one of ordinary skill in the art can assay biological samples to identify disease specific candidate biomarkers using a combination of prognostic assays to further determine and confirm diagnoses of liver diseases because they are art known and established methods that have are easily reproducible and routine in the art, see all documents.
It would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to establish more than one method of evaluating cirrhosis and additional liver diseases with a combination of techniques, such as measuring additional candidate liver diseases biomarkers and imaging analyses. It would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to assay a multitude of potential liver diseases biomarkers and image the liver via an imaging technique to further yield definitive and discriminate results indicative of distinct liver diseases, as well as progression of liver diseases, see both documents in their entireties. Ando also notes periodic ultrasound provides good information regarding stage of liver disease, see page 647, last paragraph.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings in all references that one of ordinary skill in the art can assay biological samples to identify disease specific candidate biomarkers using a combination of prognostic assays to further determine and confirm diagnoses of liver diseases because they are art known and established methods that have are easily reproducible and routine in the art, see all documents.
Double Patenting
18. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
19. The nonstatutory double patenting rejection of claims 59-71 as being unpatentable over claims 1-13 of U.S. Patent No. 10,495,643 B2 (issued December 3, 2019/ IDS U.S. Patents reference #1 on sheet 1 submitted January 16, 2024) is maintained.
Applicant asserts “…the present double patenting rejection is mooted by the amendments to the claim presented [in the Amendments to the Claims submitted November 19, 2025]”, see page 10 of the Remarks submitted November 19, 2025.
While the claims have been amended, they both continue to read on arriving at a quantifiable measure, wherein at least two of the cited biomarkers, a set is immunoassayed and if these measures exceed the normal level of the measures, the patient is diagnosed with a liver disease and a therapeutic agent should be administered. Hence, the rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims read on detecting a liver disease comprising measuring levels of a set of biomarkers in a patient’s test sample and comparing these levels to the same biomarker set levels in a control sample to determine a liver disease and differentiate between liver diseases and administer a treatment. Both sets of claims also read on a method of imaging the liver to determine the presence or absence of a liver disease in combination with the comparison of the biomarker set between the two different samples, the patient’s and the control.
Conclusion
20. 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.
21. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached between the hours, 8AM-8PM, Monday through Friday.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
Alana Harris Dent
26 January 2026
/Alana Harris Dent/
Primary Examiner, Art Unit 1643