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 .
The claims dated 11/24/2025 are under consideration.
Election/Restrictions
Applicant's election with traverse of Group III, claim 18, in the reply filed on 11/24/2025 is acknowledged. The traversal is on the ground(s) that the special technical feature of using an ovarian cancer diagnostic panel consisting of the two miRNA biomarkers miR-1246 and miR-150-5p (p. 7 of 10). The Remarks argue Chen merely reports the individual expression of various miRNAs across different disease conditions without presenting any joint evaluation of miR-1246 and miR-150-5p and does not present any data, analysis, or interpretation that connects miR-1246 and miR-150-5p as an ovarian cancer diagnostic panel (p. 8 of 10). The Remarks argue there is no rationale provided in Chen that would motivate a person of ordinary skill in the art (POSA) to select the recited miRNAs from the broad lists of miRNAs described therein, and further subsequently combine them for any diagnostic purpose, let alone for ovarian cancer diagnostic purposes (p. 8 of 10). The Remarks argue the Applicant's invention is based on the critical and non-obvious finding that the simultaneous assessment of miR-1246 and miR-150-5p together as the diagnostic panel provides a unique and highly specific molecular signature characteristic of ovarian cancer and while individually these miRNAs may show altered expression in several diseases with low specificity, only their combined diagnostic pattern provides a reliable and highly specific characterization allowing for ovarian cancer diagnosis (p. 8 of 10).
The arguments are not found persuasive because while Group I specifies a “panel consisting of two miRNA biomarkers: miR-1246 and miR-150-5p”, Groups II, III and IV are not limited in the same manner. For example, claim 18 is not limited to only determining the expression level of miR-1246 and miR-150-5p nor does it exclude additional miRNAs along with the “panel of two miRNA biomarkers”. Thus, a “panel consisting of two miRNA biomarkers: miR-1246 and miR-150-5p” is not a technical feature shared by each of the groups. A combination of RNAs that include miR-1246 and miR-150-5p is common technical feature, which does not make a contribution over the prior art of Chen or Todeschini (Cancer Letters. 2017. 388:320-327 and Supplementary Materials).
The requirement is still deemed proper and is therefore made FINAL.
Claims 1, 3-8, 14-15 and 21-29 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. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/24/2025.
Priority
The present application is a 371 national stage entry of PCT/PL21/50079 (filed 11/11/2020) and claim foreign priority to POLAND P.435967 (filed 11/12/2020).
An English translation of the foreign priority document has not been received.
The foreign priority document was filed after the ‘079 PCT application, and priority is not recognized. The earlier effective filing date for the present application is 11/11/2020.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout 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 or cited on a submitted IDS, they have not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the specification discloses nucleotide sequence at least on page 33.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). On page 33, nucleotide sequences are disclosed with no corresponding SEQ ID NO.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. The hyperlinks appear on pages 2, 18, 21, 23, 26, 31 and 34.
The use terms, such as Qubit™, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear 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
Claim 18 is objected to because of the following informalities: the claim lacks a colon or some other punctuation after the preamble of the claim. Appropriate correction is required.
Claim Interpretation
Claim 18 states “wherein the comparison provides an indicator of the subject's response to the ovarian cancer treatment for adjustment of the ovarian cancer treatment”. The recitation states a result that flows from making the comparison. It is noted the claim does not require an active method step of “indicating the subject’s response to the ovarian cancer treatment” and/or “adjusting the ovarian cancer treatment”.
It is noted the claim does not require an active method step of “determining levels of the miRNA biomarkers before ovarian cancer treatment”.
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.
Claim 18 is rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more.
Claim 18 recites a series of steps and therefore is a process.
The claim(s) recite(s):
“determining the expression level of a panel of two miRNA biomarkers: miR-1246 and miR-150-5p in a sample from a subject after the ovarian cancer treatment”;
“comparing the levels determined in step i) with the expression levels of miR-1246 and miR-150-5p in the subject before ovarian cancer treatment”; and
“the comparison provides an indicator of the subject's response to the ovarian cancer treatment for adjustment of the ovarian cancer treatment”.
The “determining” step broadly encompasses an abstract in view of the specification. The specification describes “normalization” or analysis, manipulating or processing of raw data a being how expression levels are determined. See p. 4, 5. The “normalization” process is based on a formula, i.e., a mathematical formula, which is an abstract idea.
The “comparing” step broadly encompasses comparing four data points. This limited amount of data may be compared purely in the human mind and thus encompasses an abstract idea.
The statement regarding what the “comparison provides” broadly sets forth a natural correlation between the levels of the miRNA biomarkers and the subject’s response to treatment.
The judicial exceptions are not integrated into a practical application because the claims do not involve:
improvements to the functioning of a computer or to any other technology or technical field;
applying or using the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition;
applying the judicial exception with, or by use of, a particular machine; or
effecting a transformation or reduction of a particular article to a different state or thing.
The claimed limitations add insignificant extra-solution activity to the judicial exceptions as they broadly encompass data gathering steps. While claim 18 further comprises “treating the subject based on the indicator of the subject's response to the ovarian cancer treatment”, the treating is not particular in any manner. The step is recited at a high level of generality such that it amounts to instructions “to apply” the judicial exceptions. Furthermore, the step is premised on the “indicator”; however, the claim does not require any active method steps of “indicating the subject’s response to the ovarian cancer treatment” and/or “adjusting the ovarian cancer treatment”. Thus, there is no nexus between the above judicial exceptions and the treating step.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims encompass the use of techniques that are well-known and used in a conventional manner as described on pages 10, 12 and 15 of the instant specification.
Claim Rejections - 35 USC § 112
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.
Claim 18 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
While the instant specification analyzes miRNA levels in serum samples, the claims are not enabled for any type of sample as broadly encompassed by and used in the claims.
The specification notes that miRNA levels vary between serum and tissues (p. 3).
The instant specification analyzes a serum sample from blood (p. 15). No other tissues or biological samples are analyzed for miRNA levels that are relevant in the context of ovarian cancer. Thus, without additional evidence, the ordinary artisan would not have reasonably extrapolated the levels of miRNA observed in serum to any and all other types of samples.
The claim is not fully enabled for the type of sample in which the level of the miRNA biomarkers are determined or for comparisons between levels of miRNA biomarkers determined in one type sample prior to treatment and a different type of sample after treatment.
Amending the claims to specify the miRNAs levels before and after treatment are determined in serum samples.
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.
Claim 18 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.
Regarding claim 18, the claim specifies comparing the determined levels with “the expression levels of miR-1246 and miR-150-5p in the subject before ovarian cancer treatment”. The recitation lacks proper antecedent and the claim is incomplete because “expression levels” are not determined, provided or obtained prior to treatment.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Todeschini (Cancer Letters. 2017. 388:320-327 and Supplementary Materials) and Lodes (WO 2010/098862 A2).
Regarding claim 18, Todeschini teaches determining the levels of miRNAs prior to ovarian cancer treatment (p. 321, patients, and miRNA profiling by microarray). Todeschini found hsa-miR-1246 and hsa-miR-150-5p to be differentially expressed between tissue from HGSOC patients and healthy controls (Table S3.1).
These miRNAs may be used to distinguish HGSOC samples from normal tissues based on the differential expression.
Lodes teaches the miRNA content of ovarian tumor cells could be used to distinguish cancer patients from patients with benign ovarian disease and from normal controls. Lodes further teaches the use of miRNA expression patterns as a biomarker to monitor the effect of therapy on cancer progression (p. 5 to 6).
It would have been prima facie obvious to the ordinary artisan at the time of filing to have used the miRNAs of Todeschini to monitor whether HGSOC cells are present over the course of ovarian cancer treatment. For example, one would monitor the miRNA levels prior to treatment to have an established baseline regarding the ovarian tumor miRNA levels. By measuring the levels of miRNAs after the start of treatment, one would be able to gauge the progression of the ovarian cancer. For example, if the levels changed and looked more like benign or normal tissue, one would conclude the treatment was working or had worked. Alternatively, if the levels did not change, one would reasonably conclude the treatment was not working as ovarian tumor cells were still present. Based on whether or not ovarian tumor cells are present, one would be able to adjust the treatment accordingly.
Conclusion
No claim allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682