DETAILED ACTION
The present Office Action is responsive to the Amendment received on June 29, 2026.
Preliminary Remark
Claims 10, 15, 16, and 19-114 are canceled.
Claim Objections
The objection made to claim 11 for reasons noted in the Office Action mailed on March 30, 2026 is withdrawn in view of the Amendment received on June 29, 2026.
Claim Rejections - 35 USC § 112
The rejection of claims 1-20 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particularly point out and distinctly claim the subject matter, made in the Office Action mailed on March 30, 2026 is withdrawn in view of the Amendment received on June 29, 2026.
Rejection – New Grounds, Necessitated by Amendment
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 1-9, 11-14, 17, and 18 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.
Claim 1 is indefinite because it is unclear how the level of the extracellular vesicles (not the target biomarker) are utilized in the assay. This is because the extracellular vesicles are first captured via cell-surface antigen which is not specific for the biomarkers being analyzed. Simply determining the level of the captured extracellular vesicles by this process cannot result in determination of cancer as claimed. For the purpose of prosecution, the level of the biomarkers present in the extracellular vesicles (not the vesicles) is construed as being utilized for the determination/classification step.
Claim 2 is indefinite for reciting the phrase, “the at least one target biomarker” as there is no longer a sufficient antecedent basis for the phrase. The phrase has been construe to mean, “the at least one further biomarker” as now provided by parent claim 1.
Claim 5 is indefinite because the term, “the first … target biomarker” no longer is supported by an antecedent basis.
Claims 17 and 18 are indefinite because they depend from a canceled claim (i.e., claim 15).
For the purpose of prosecution, these claims have been construed to depend from claim 1.
Claim 17 is also indefinite as the parent claim has been amended to recite the use of qPCR, when the parent claim 1 has been amended to recite that the determination involves PLA which is an antibody-mediated detection means.
Claims 2-9, 11-14, 17, and 18 are rejected by way of their dependency on claim 1.
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.
Claims 1-9, 11-14, 17, and 18 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. 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. This is a New Matter Rejection.
The sole independent claim has been amended to recite a step of detecting via means of a proximity ligation assay for at least one biomarker, wherein the biomarker is recited as being RNAs. The use of PLA in the art is employed with antibody-oligonucleotide conjugate, wherein the at least a pair of antibodies bind to their target in “proximity” to each other, with their oligonucleotide conjugates being ligated to each other for added specificity of detection. The Office is not aware of PLA that exists for detecting RNAs. Applicants are welcomed to point to the specification where such examples are discussed.
Claims 2-9, 11-14, 17, and 18 are dependent on claim 1 and therefore, include new matter by way of their dependency.
Claim Rejections - 35 USC § 101
The rejection of claims 10, 15, 16, 19, 20 under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception of natural phenomenon without significantly more, as discussed in the Office Action mailed on March 30, 2026 is withdrawn in view of the Amendment received on June 29, 2026, canceling the rejected claims.
Rejection - Maintained
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.
The rejection of claims 1-9, 11-14, 17, and 18 under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception of natural phenomenon without significantly more, as discussed in the Office Action mailed on March 30, 2026, is maintained for the reasons of record.
Applicants’ claim amendment and arguments presented in the Amendment received on June 29, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
The Rejection:
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.
Response to Arguments:
Applicants traverse the rejection.
Applicants contend that the amendment made to claim 1 renders the claim patent eligible because the claim is no longer recited in generic terms. Specifically, Applicants contend that the steps of immunoaffinity capture of extracellular vesicles on a solid substrate via a target-capture moiety directed at a defined surface biomarker; resolution at the level of individual captured vesicles rather than bulk sample; and proximity ligation as the detection chemistry now provides a specific assay architecture and not to the natural correlation between biomarker levels and disease (page 8, Response).
This argument has been carefully considered but have not been found persuasive.
The Office contends that the recited steps are not deemed to add significantly more than the judicial exception that exists between the biomarkers and liver cancer.
While the claims may have recited the additional steps that captures the extracellular vesicles, and the assay of at least one biomarker from said extracellular vesicles via a method described as “proximity ligation assay,” the steps of sample capture and analysis of the contents therein (i.e., biomarkers) via a step of “proximity ligation” is as generic as a method which attempt to tie the naturally existing correlation by reciting the steps of cell lysis, and detection of the biomarkers via PCR with primers. Such recited additional elements are deemed insufficient because these are pre-solution activity which is generically recited in order to capture the judicial exception, the means of which are well-known, routine and convention in the art of molecular diagnostics.
While Applicants contend that in CellzDirect, the court held that a method of employing a natural property of hepatocytes to survive freeze-thaw cycles was patent eligible because the claim recited a specific technique that produced a useful result and not a mere observation of the natural phenomenon, which was “directed to a new and useful method of preserving hepatocyte cells” (page 8, Response), the Office does not see a corollary to the instant claims. This is because the instantly claimed invention is not directed to a new and useful method of detecting the biomarkers. Rather, the invention is directed to the discovery of the naturally existing correlation, wherein the means to identify the naturally existing correlation employs means which are generally applicable in the art of molecular diagnostics, thus well-known, routine, and/or conventional. In CellzDirect, the means of detection was new and useful. In the present case, the means of detection is not new. Rather, the means are routine pre-solution activity that are conventionally employed in the art, which reveals the naturally existing correlation.
Therefore, Applicants’ arguments are not found convincing and the invention as claimed is deemed to lack patent eligibility.
Conclusion
No claims are allowed.
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.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YOUNG J KIM/Primary Examiner
Art Unit 1637 September 9, 2026
/YJK/
Prosecution Insights