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 .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 4-6, drawn to a method of providing information necessary for diagnosing hepatocellular carcinoma in the reply filed on 18 February 2026 is acknowledged.
Claims 1-3 and 7-8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 18 February 2026.
Information Disclosure Statement
The information disclosure statement (IDS) filed 24 May 2023 is considered, initialed, and attached hereto.
Claim Status
Claims 1-8 are pending. Claims 4-6 are under examination. Claims 1-3 and 7-8 are withdrawn.
Specification
The use of the term SeraMir, ExoQuick, Nano Drop, TRIzol, Invitrogen, PrimeScript, miScript, QIAGEN, Microsoft, and MedCalc, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 4 and 5 objected to because of the following informalities: the usage of (1), (2), and (3) to denote steps in claim 4 and to denote step (3) in claim 5 may introduce confusion as to whether these denote steps or claims. Using a different system to denote steps, such as A), B), C) or (i), (ii), (iii) would resolve this objection. Appropriate correction is required.
Claim Interpretation
The recitation “necessary for diagnosing hepatocellular carcinoma” in claim 4, lines 1-2 is an intended use of the invention recited in the preamble. MPEP §2111.02 II. states: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. As the body of the claim sets forth clear and full steps describing the claimed process, the recitation “necessary for diagnosing hepatocellular carcinoma” does not carry patentable weight.
Claim Rejections - 35 USC § 112(b) - Indefiniteness
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.
Claim 5 is 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 5 recites “the operation (3) is performed by a cut-off value which has a Ct value (threshold cycle) of 0.85 for the SF3B4” and depends on claim 4, which recites “(3) determining as hepatocellular carcinoma when the measured expression level of SF3B4 is higher than that of the control sample”. It is unclear how the cut-off value performs the operation of determining as a value is a piece of data and not an agent capable of performing operations. Additionally, it is unclear what it means for a cut-off value to have or possess a Ct value (e.g. is the cut-off value a collection of values including a Ct value, is it derived from a Ct value?). This lack of clarity makes it impossible for one of ordinary skill in the art to ascertain the metes and bounds of claim 5. Based on the inclusion of the phrase “a Ct value (threshold cycle) of 0.85 for the SF3B4”, for the purpose of examination claim 5 is interpreted as requiring that the measured expression level of SF3B4 is not just higher than that of the control sample (as inherited by depending on claim 4), but that the sample isolated from a patient has a measured Ct value of 0.85 for SF3B4 (i.e. the amplification plot for SF3B4 must cross the threshold after 0.85 cycles of amplification).
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 4-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature (natural correlation) and an abstract idea without significantly more. The claims recite “comparing the measured expression level” and “determining as hepatocellular carcinoma when the measured expression level of SF3B4 is higher than that of the control sample”. The following inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim to a process, machine, manufacture, or composition of matter? Yes, the claims are directed to processes.
Step 2A, prong 1. Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)? Yes, where the claims recite the acts of comparing the measured expression level and determining as hepatocellular cancer, these concepts are abstract ideas as they can be performed in one’s head by a skilled person looking at data. Where the claims recite the correlation of hepatocellular carcinoma with the measured expression of SF3B4 in the blood-derived serum exosome sample being higher than that of a control sample, this concept is a recitation of a law of nature (natural correlation).
Step 2A, prong 2. Does the claim recite additional elements that integrate the exception into a practical application? No, the judicial exceptions to which the claims are directed are not integrated into a practical application because the rejected claims do not require any particular practical steps that are not considered extra-solution activity due to being mere data gathering, such as measuring an expression level from a sample (MPEP §2106.05(g), an example of mere data gathering includes “Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968)”). The additional element of a Ct value of 0.85 used in claim 5 to define the natural correlation between SF3B4 expression and hepatocellular carcinoma does not integrate the exception into a practical application because it merely defines a more limited version of the natural correlation.
Step 2B. Does the claim recite additional elements that amount to significantly more than the judicial exception? No, the claims include the practical step of measuring an expression level of SF3B4, but the broadly recited step is properly considered routine and conventional and is mere data gathering, so the claims are not significantly more than the judicial exceptions to which they are directed. The additional element of a Ct value of 0.85 used in claim 5 to define the natural correlation between SF3B4 expression and hepatocellular carcinoma does not amount to significantly more than the judicial exceptions because it merely defines a more limited version of the natural correlation.
For these reasons, claims 4-6 are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
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 nonobviousness.
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 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Nam et al. (WO 2019/146841, published 8 January 2019), herein Nam, in view of Soung et al. ("Exosomes in Cancer Diagnostics" Cancers, 9(1): 8 (2017)), herein Soung.
Regarding claim 4, Nam teaches a method of providing information for diagnosing hepatocellular carcinoma, comprising: (1) measuring an expression level of SF3B4 from a blood serum sample isolated from a patient (“The method of measuring the expression level or protein level of […] SF3B4 […] in the above can be performed by a known process for detecting or isolating mRNA or protein from a biological sample […] the “biological sample” refers to […] blood, serum” FIT Translation page 15); (2) comparing the measured expression level of SF3B4 with a control sample (“comparing the measured expression levels of […] SF3B4 with the expression levels of the corresponding genes of the control sample” FIT Translation page 15); and (3) determining as hepatocellular carcinoma when the measured expression level of SF3B4 is higher than that of the control sample (“the expression level of […] SF3B4 is determined to be higher than the expression level of the control sample to determine that the liver cancer has occurred” FIT Translation page 6; see also Figure 6b, eHCC indicates early hepatocellular carcinoma, NL indicates normal liver tissue, DN indicates dysplastic nodule, this shows higher SF3B4 expression in hepatocellular carcinoma than controls). However, Nam does not teach that the blood sample is a blood-derived serum exosome sample. This deficiency is made up for in the teachings of Soung.
Regarding claim 4, Soung teaches the isolation of exosomes from blood serum (“exosomes from blood serum were successfully isolated” page 2 para 2) and using isolated exosomes for diagnosis of cancer (“cancer derived exosomes likely serves as biomarker for early detection of cancer as they carry the cargo reflective of genetic or signaling alterations in cancer cells of origin” page 1 last para). Soung also teaches that the use of exosome samples is advantageous over conventional tissue samples because it provides a more convenient and non-invasive way of diagnosis than the surgery required for tissue biopsy (page 1 last para).
Regarding claim 6, Nam teaches a method of providing information for diagnosing hepatocellular carcinoma wherein the hepatocellular carcinoma is early stage hepatocellular carcinoma (“method for providing information for the diagnosis of early liver cancer” FIT Translation page 6; see also Figure 6b, eHCC is early hepatocellular carcinoma).
In view of Soung’s teaching that using an isolated exosome sample for cancer diagnosis is advantageous over tissue samples because it provides a more convenient and non-invasive method of diagnosis, one of ordinary skill in the art would be motivated to combine the method of diagnosing hepatocellular carcinoma taught by Nam with the method of using exosomes taught by Soung. One of ordinary skill in the art would have a reasonable expectation of success in this combination because Nam teaches using blood serum as its sample and Soung teaches isolating exosomes from blood serum, so the combination merely adds an additional step of processing the blood serum sample, and because Soung teaches that cancer derived exosomes carry cargo reflective of the genetic alterations in cancer cells of origin. Therefore, the invention as a whole of claims 4 and 6 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Rejected Claims Free of the Prior Art
Claim 5 is free of the prior art under the interpretation used for the purpose of examination (see rejection of claim 5 under 35 U.S.C. 112(b)) as requiring that the measured expression level of SF3B4 have a Ct value of 0.85. While both Nam and Seong teach using qRT-PCR to detect nucleic acid biomarkers, which would yield Ct values, they do not teach a Ct value of 0.85 or a Ct value near enough that a Ct of 0.85 would be obvious. It is noted here that Ct is the cycle number that the amplification plot crosses a threshold value of fluorescence in qRT-PCR assays. A Ct of 0.85 means that the threshold was passed in under one cycle of amplification of the template. While one of skill in the art could obtain such a Ct by manually adjusting the threshold value, the art does not teach any reason to adjust the threshold to obtain a Ct this low.
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jeffrey Lawrence Bellah whose telephone number is (571)272-1024. The examiner can normally be reached M-Th, 7:30-5 ET.
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/JEFFREY BELLAH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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