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 .
Information Disclosure Statement
The IDS received on August 4, 2025 is proper and is being considered by the Examiner.
Drawings
The drawings received on January 18, 2024 are acceptable.
Claim Objections
Claim 11 is objected to because of the following informalities: claim 11 needs a space in the phrase, “sample)with a capture…”
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 1-20 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 1, 8, 9, and 11 recite a parenthetical limitation with “e.g.”, which renders the claim indefinite in whether or not the limitations are an actively required limitation. Removal of all such recitation is suggested.
Claim 1 is also indefinite for missing a conjunction between steps (c) and (d). For the purpose of prosecution, the conjunction, “and” has been assumed.
Claim 5 recites the phrase, “the first and/or second target biomarker signature…” The phrase lacks an antecedent basis for the second target biomarker signature” as the claim depends from claim 1.
Claims 7 and 17-19 are indefinite for the same reason as claim 5.
Claim 6 recites the phrase, “the at least two biomarkers.” There is an insufficient antecedent basis for this limitation in the claim.
Claims 2-20 are also indefinite by way of their respective rejected parent claims, as well as based on their dependency on the sole independent claim 1.
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception of natural phenomenon without significantly more. The claims recite the naturally existing correlation of biomarkers found in a host and their levels associated with a host’s (i.e., subject) predisposition to developing or having liver cancer. This judicial exception is not integrated into a practical application because recited additional elements/steps of the claims are not significantly more than the judicial exception itself.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception based on the analysis under the current Patent Eligibility Guidelines (herein, “PEG”) as discussed below.
Step 1 Inquiry under PEG
Step 1 inquiry under Patent Eligibility Guidelines (herein, “PEG”) determines whether or not the claimed invention is drawn to one of the recognized statutory classes of invention. Claims 1-20 satisfy the present inquiry as being drawn to a method.
Step 2A Inquiry under PEG
A recently revised PEG now performs step 2A inquiry under a 2-prong analysis, and the subject claims analyzed accordingly as follows:
Prong 1:
Prong-1 inquiry under step 2A determines whether the claim(s) recites an abstract idea, a law of nature, or a natural phenomenon. As stated above, the claims recite the judicial exception that captures the naturally existing phenomenon of biomarker levels with predisposition to develop/have liver cancer. Therefore, claim recites a judicial exception.
Prong 2:
Prong-2 inquiry under step 2A determines whether or not the claims recite additional elements that integrate the judicial exception into a practical application in a manner that imposes a meaningful limit on the judicial exception.
The following additional elements are observed:
A - Comparison to a classification cutoff reference:
Claims recite that the levels of the recited markers in the subject is compared against a cut off value from a reference. The specification describes classification cutoff as that which refers to a level, value or a score used in prediction (see section [0088], specification).
However, establishing a cutoff value derived from the expression level of markers in normal, non-cancerous samples is not deemed to impose a meaningful limit on the judicial exception because the step simply reveals the levels of expression in a subject’s sample against a known standard, which is standard practice in the field of molecular diagnostics.
B – Size exclusion treatment of the samples:
Some claims recite that the fluid derived sample is subjected to size-exclusion treatment so as to analyze the markers from extracellular vesical associated surface biomarker. However, performing size-exclusion treatment has been a well-established means for obtaining materials of wanted size.
According to MPEP 2106.04(d)(2)(c), providing a necessary precursor step for use of recited exception is considered an extra-solution activity:
“consider a claim that recites (a) administering rabies and feline leukemia vaccines to a first group of domestic cats in accordance with different vaccination schedules, and (b) analyzing information about the vaccination schedules … Step (b) falls within the mental process grouping of abstract ideas … While step (a) administers vaccines to the cats, this administration is performed in order to gather data for the mental analysis step, and is a necessary precursor for all uses of the recited exception. It is thus extra-solution activity, and does not integrate the judicial exception into a practical application.” (MPEP 2106.04(d)(2)(c))
Similarly, the step of performing a size-exclusion step is a necessary precursor step which allows the judicial exception to be observed, and therefore, deemed an extra-solution activity.
C – Means of detection:
Some claims recite the additional elements directed to the means of detecting the biomarkers in the form of a capture assay involving a solid substrate, such as beads, antibody capture, qPCR, and permeabilization of the samples.
However, these are also considered to be an extra-solution activity captured by generic language, which are routinely performed in the art for the purpose of observing the judicial exception, and therefore, fail to add significantly more to the claimed judicial exception.
As explained by the Supreme Court, in order to transform a judicial exception into a patent-eligible application, the additional element or combination of elements must do ‘more than simply stat[e] the [judicial exception] while adding the words ‘apply it’”. Alice Corp. v. CLS Bank, 573 U.S. __, 134 S. Ct. 2347, 2357, 110 USPQ2d 1976, 1982-83 (2014) (quoting Mayo Collaborative Servs. V. Prometheus Labs., Inc., 566 U.S. 66, 72, 101 USPQ2d 1961, 1965). Thus, for example, claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 134 S. Ct. at 2358, 110 USPQ2d at 1983. See also 134 S. Ct. at 2389, 110 USPQ2d at 1984 (warning against a § 101 analysis that turns on “the draftsman’s art”) (MPEP 2106.05(f))
Step 2B Inquiry under PEG
Step 2B inquiry of the PEG determines whether or not additional elements are provided and whether such elements amount to significantly more than the judicial exception in the claims.
The additional elements discussed above, are recited with highly generic language, directed to means which are routinely employed and conventional in the art of molecular diagnostics, and therefore, are not deemed to add significantly more.
Therefore, the present claims lack patent eligibility.
Conclusion
No claims are allowed.
Brown et al. (WO 2012/174282 A2, published December 2012) is a relevant prior art that teaches the motivation to perform multi-omic assay for cancer determination, teaching that biomarkers of DNA, RNA, and proteins can provide a signature from which phenotypes can be determined:
“identification of specific biomarkers, such as DNA, RNA and proteins, can provide biosignatures that are used for the diagnosis, prognosis, or theranosis of conditions and diseases” (section [0008])
“characterizing a phenotype by analyzing circulating biomarkers such as a vesicle, microRNA, or protein present in a biological sample … phenotype for a subject or individual may include, but is not limited to the diagnosis of a disease or condition, the prognosis of a disease or condition, the determination of a disease stage or a condition stage, a drug efficacy …” (section [0011])
“biosignatures can be used in the … identifying whether a subject suffering from cancer is a likely responder or non-specific respond to a particular cancer treatment … liver cancer …” (section [0504])
The artisans also teach that various sources of samples can be assayed, such as those from bodily fluids, including microvesicles (“circulating DNA, RNA, proteins, and vesicles … mRNA … circulating vesicles … membrane encapsulated structure that are shed from cells and have been found in a number of bodily fluids, including blood, plasma, serum …”, section [0008]).
“[b]iosignatures can be detected using capture agents and detection agents … a vesicle having a cell-of-origin specific antigen on its surface and a cancer-specific antigen on its surface … can be captured using an antibody” (section [0406])
“one or more biomarker comprises a messenger RNA (mRNA)” (section [0014])
Brown et al., however, do not teach the use of the biomarker or its combination as recited in claim 1 that is produced from extracellular vesicles whose expression correlate to liver cancer.
Sedlak et al. (WO2020/180741 A1, published September 2020) also evidences the same knowledge as discussed above. The artisans, however, fail to teach the recited biomarkers as present claimed.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 March 26, 2026
/YJK/
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