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 amended claims dated 2/5/2026 are under consideration.
The 2/5/2026 claims are not properly annotated in regards to the amendments made. For example, previous claim 1 had steps b), c) and d); however, amended claim 1 has steps a) and b), without indicating where step c) and d) were deleted. In fact, it is noted that the deleted “comparing step” is identified as step b) rather than step d).
In the interest of compact prosecution, the claims dated 2/5/2026 will be considered.
Applicant is reminded to properly annotate claim amendments in future responses.
The amendments and arguments presented in the papers filed 2/5/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 10/22/2025 listed below have been reconsidered as indicated.
a) The amendments to the specification addressing trade name or mark usage are acknowledged.
b) The objection of claim 1 is withdrawn.
c) The rejections of claims 1-7 and 11-13 under 35 U.S.C. 101 are withdrawn because the claim requires to tangible, active method steps of “determining the expression level” of at least one gene in isolated samples of ovarian tissue, blood or urine.
d) The rejections of claims 1-7 and 11-13 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in view of the amendments to the claims.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Election/Restrictions
Applicant elected Group I in the reply filed on 9/22/2025 and Group II was rejoined.
In view of the withdrawal of the restriction requirement between Groups I and II, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
The election of species requirement between regarding a single combination of genes was previously withdrawn.
Applicant elected determining expression level of genes at the nucleic acid level in the reply filed on 9/22/2022. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election was treated as an election without traverse (MPEP § 818.01(a)).
Claims 8, 9, 10, 14 and 15 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 9/22/2025.
Priority
The present application is a 371 national stage entry of PCT/IB2021/054315 (filed 05/19/2021), which claims priority to ITALY 102020000011977 (filed 5/21/2020).
It is noted an English translation of the certified foreign priority document has not been received.
Claim Objections
Applicant is advised that should claim 2 be found allowable, claim 4 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Both claim 2 and 4 limit the “at least one gene and/or of said at least one protein encoded by said at least one gene in one or more isolated sample” to EPCAM, ESRP1, GPR56/ADGRG1, MAL2, MYH14, PRSS8, ST14 and WFDC2.
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.
Claims 1, 2, 3, 4, 6 and 11 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 following are new rejections necessitated by the amendments to the claims.
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.
Regarding claim 1, the claim encompasses “determining the expression level of said at least one protein encoded by said at least one gene in one or more isolated sample”. The claim also states “step a) is carried out on a digital, targeted multiplex nucleic acid analysis system for gene expression/profiling of RNA and or DNA”. The instant specification does not describe how to determine the expression of a protein using a system for the gene expression/profiling of nucleic acids.
The ordinary artisan would not have found applicant in possession of methods using a system for the gene expression/profiling of nucleic acids in determining the expression of proteins.
Claims 2-4, 6 and 11 depend from claim 1 and are rejected for the same reason.
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.
Claims 1, 2, 3, 4, 6 and 11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
The following rejections have been maintained.
The specification, while being enabling for methods of claims 1 and 4 in which the isolated samples and reference samples are ovarian samples with nucleic acids, does not reasonably provide enablement for making a diagnosis or prognosis based on the protein expression levels. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The claimed method broadly encompass determining the expression level of at least one of the recited genes at the protein or nucleic acid levels. The instant specification only analyzed RNA expression in ovarian tissues.
It is also known that levels of protein in a cell is not necessarily reflective of the mRNA levels of a cell. See Maier (FEBS Letter. 2009. 583:3966-3973; previously cited); Kendrick (A gene’s mRNA level does not usually predict its protein level. 9/25/2014; previously cited); Chan (G&P magazine. 2006. 6(3):20-26; previously cited); Chen (Molecular & Cellular Proteomics 1.4. 2002. 1:304-313; previously cited); and Greenbaum (Genome Biology. 2003. 4:117; previously cited).
It is unpredictable that the results of the specification can be extrapolated to making a diagnosis or prognosis based on protein levels observed. It would require undue experimentation, with no reasonable expectation of success, to establish that the nucleic acid expression level observed in ovarian tissue can be applied to protein levels.
Examiner’s Response to the traversal of the 112(a) rejections
The Remarks argue the claims have been amended to specify the types of samples rendering the rejections moot (p. 12).
The arguments have been considered but they fail to address the above issue raised previously.
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, 2, 3, 4, 6 and 11 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.
The following rejections have been maintained from the previous Office action.
Regarding claim 1, it is not clear how the recited preamble is intended to breathe life and meaning into the claims. The preamble of the claim recites a method for carrying out an in vitro diagnosis of ovarian cancer in a subject. However, the method steps in the claim only requires two step of determining expression levels in two isolated samples. Thus, it is unclear if applicant intends to cover any method of performing these steps, or if the method is intended to somehow require more to accomplish the goal set forth in the preamble. If it is the later, then it appears that the claims are incomplete, as they fail to provide any active steps that clearly accomplish the goal of “carrying out…diagnosis of ovarian cancer in a subject” as set forth by the preamble of the claim. Amending the claim to include an active process step directed towards diagnosing ovarian cancer in the subject based on the determined expression level. Claims 2, 3, 4, 6 and 11 are similarly indefinite because they directly or indirectly depend from claim 1.
Regarding claim 3, the claim recites “said further genes” in line 3. The recitation lacks proper antecedent basis.
The following are new rejections necessitated by the amendments to the claims.
Regarding claim 1, the recites “said at least one gene” in line 3, “said at least one protein” in lines 3-4, “said at least one gene” in line 4, “said at least one gene” in line 5, “the at least one protein” in line 6, and “said at least one gene” in line 6.Each of the recitations lacks proper antecedent basis.
Examiner’s response to the traversal of the 112(b) rejections
The Remarks argue the amendments render moot the 112(b) rejections (p. 12).
The claims remain rejected for the reasons provided above.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 2, 3, 4, 6 and 11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wamunyokoli (Clin Cancer Res. 2006. 12(3):690; previously cited).
Claim 1 is drawn to a method for “carrying out an in vitro diagnosis of ovarian cancer in a subject”. However, the active method steps do not explicitly require making any diagnosis. MPEP 2111.02 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.
Accordingly, the claim language of the preamble merely sets forth the intended use or purpose of the claimed methods, but does not limit the scope of the claims. The claims are given the broadest reasonable interpretation as requiring: determining the expression level of said at least one gene and/or of said at least one protein encoded by said at least one gene in one or more isolated sample; and b) determining the expression level of said at least one gene and/or of the at least one protein encoded by said at least one gene from one or more isolated reference samples.
Regarding claims 1, 2, 3, 4 and 6, Wamunyokoli teaches determining and RNA expression levels of at least one gene using the U133 Plus 2.0 Gene Chip oligonucleotide array in:
an isolated sample from a subject, e.g., cystadenomas, LMP tumors or adenocarcinomas as encompassed by “one or more isolated sample”; and
normal tissue, e.g. normal ovarian surface epithelium brushings, or a different type of ovarian cancer as encompassed by an “isolated reference samples”.
See p. 691, Tissue samples; Table 2; p. 695.
The at least one gene having its expression levels determined in the samples included the following:
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The gene information is provided in the Supplementary Data of Wamunyokoli and is presented as a table derived by the examiner from the Supplementary Data.
The U133 Plus 2.0 Gene Chip oligonucleotide array is broadly encompassed by a “digital, targeted multiplex nucleic acid analysis system for gene expression/profiling of RNA and/or DNA” because it converts biological samples into digital data by capturing target nucleic acids using oligonucleotides in a multiplex manner and reading signals with a scanner.
Claim 1 includes a “wherein” clause that sets forth an intended use of the determined expression levels. The clause does not require any additional active method steps.
Alternatively, the claims are rejected as detailed below.
Regarding claims 1, 2, 3, 4, 6 and 11, Wamunyokoli teaches determining the RNA expression levels of numerous genes using the U133 Plus 2.0 Gene Chip oligonucleotide array in:
an isolated sample from a subject, e.g., cystadenomas, LMP tumors or adenocarcinomas as encompassed by “one or more isolated sample”; and
normal tissue, e.g. normal ovarian surface epithelium brushings, or a different type of ovarian cancer as encompassed by an “isolated reference samples”.
See p. 691, Tissue samples; Table 2; p. 695.
The use of the U133 Plus 2.0 GeneChip oligonucleotide array gene includes using probes for determining and obtaining the expression levels of each of the genes recited in the claims as evidenced by the UCSC Genome Browser. The search results from the UCSC Genome Browser were included with a prior Office action. A list of probes for the genes was compiled by the examiner using the UCSC Genome browser is provided in the following table.
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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) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wamunyokoli (Clin Cancer Res. 2006. 12(3):690; previously cited) in view of Warren (The Journal of Targeted Therapies in Cancer. 2016. 5(2): 10 pages; previously cited).
The following is an alternative rejection of claim 1, in which a preferred embodiment of the claims are rendered obvious.
Claim 1 is drawn to a method for “carrying out an in vitro diagnosis of ovarian cancer in a subject”. However, the active method steps do not explicitly require making any diagnosis. MPEP 2111.02 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.
Accordingly, the claim language of the preamble merely sets forth the intended use or purpose of the claimed methods, but does not limit the scope of the claims. The claims are given the broadest reasonable interpretation as requiring: determining the expression level of said at least one gene and/or of said at least one protein encoded by said at least one gene in one or more isolated sample; and b) determining the expression level of said at least one gene and/or of the at least one protein encoded by said at least one gene from one or more isolated reference samples.
Regarding claim 1, Wamunyokoli teaches determining and RNA expression levels of at least one gene using the U133 Plus 2.0 Gene Chip oligonucleotide array in:
an isolated sample from a subject, e.g., cystadenomas, LMP tumors or adenocarcinomas as encompassed by “one or more isolated sample”; and
normal tissue, e.g. normal ovarian surface epithelium brushings, or a different type of ovarian cancer as encompassed by an “isolated reference samples”.
See p. 691, Tissue samples; Table 2; p. 695.
The at least one gene having its expression levels determined and obtained included the following:
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The gene information is provided in the Supplementary Data of Wamunyokoli and is presented as a table derived by the examiner from the Supplementary Data.
Claim 1 includes a “wherein” clause that sets forth an intended use of the determined expression levels. The clause does not require any additional active method steps.
While Wamunyokoli teaches the above methods, Wamunyokoli does not specifically teach the use of a commercially available nCounter® DX Analysis System platform for analyzing expression levels.
However, Warren teaches the assay was known at the time of filing and that is an FDA cleared platform for some assays (p. 4).
It would have been prima facie obvious to the ordinary artisan at the time of filing to have confirmed the results of Wamunyokoli using the nCounter® DX Analysis System platform because it is an FDA cleared assay platform.
Examiner’s response to the traversal of the prior art rejections
The Remarks argue Wamunyokoli describes results in the gene expression between different types of ovarian tumors and Wamunyokoli does not compare the gene expression of samples from normal tissue with gene expression of tissues from tumoral ovarian cancer. See p. 13-14.
The arguments have been fully considered but are not persuasive. Wamunyokoli teaches determining the expression of genes in “tumor cells and OSE brushings” that were obtained (p. 691, Microdissection). The “OSE brushings” are “normal” or “healthy” ovarian tissue. Furthermore, as acknowledged by the Remarks, Wamunyokoli describes results in the gene expression between different types of ovarian tumors, which is also encompassed by claim 1. One type of ovarian tumor is an “isolated sample” and another type is an “isolated reference sample”.
The Remarks argue claim 1 now recites the limitations of claim 13 which is not rejected for allegedly being anticipated by Wamunyokoli (p. 14).
The arguments have been fully considered but are not persuasive. Claim 13 required the specific use of the “nCounter DX Analysis System platform”, but amended claim 1 requires a generic “digital, targeted multiplex nucleic acid analysis system for gene expression/profiling of RNA and or DNA”. The array used by Wamunyokoli is encompassed by this generic system.
Regarding the 103 rejections, the Remarks argue claim 1 is patentable over the combination of the teachings of Wamunyokoli and Warren, it is respectfully submitted that claim 4 is patentable as well (p. 15).
The arguments have been fully considered but are not persuasive. Claim 1 is rejected for the reasons provided above. Claim 4 was previously an independent claim but now is a claim that depends from claim 1. Claim 4 is rejected as being anticipated by Wamunyokoli as described above.
Conclusion
No claims 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.
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.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682
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