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 .
Applicant's election with traverse of Group II in the reply filed on 8/18/25 is acknowledged. The traversal is on the ground(s) that the claims all require the analysis of mRNA expression of one of 7 genes. This is not found persuasive because at least because the detection of mRNA expression of genes in NSCLC samples was known, as evidenced by the prior art rejections here. Therefore, this feature is no a “special” technical feature.
The requirement is still deemed proper and is therefore made FINAL.
Priority
Applicant states that this application is a continuation or divisional application of the prior-filed application. A continuation or divisional application cannot include new matter. Applicant is required to delete the benefit claim or change the relationship (continuation or divisional application) to continuation-in-part because this application contains the following matter not disclosed in the prior-filed application: The instant disclosure contains examples that are not in the parent application, and further disclose and require extracting RNA from formalin fixed and paraffin embedded tumor which is not disclosed in the parent application.
The effective filing date of the instant claims is the actual filing date of this application, which is the date of the PCT filing, 3/19/2020.
Claim Objections
Claims 9 and 11 are objected to because of the following informalities: there is a typographical error where ZNF1 is recited instead of ZNF71. Appropriate correction is required.
Drawings
The drawings are objected to because the panels in figure 2(a) are illegible, they are essentially black rectangles. Furthermore, Figure 2b and 2c are not labeled as such. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: The specificaiotn on p. 26 refers to figures 5A and 5B when describing data from the ZNF1 IHC/AQUA assay, but the images in figures 5A and 5B do not match the description in the specification.
Appropriate correction is required.
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 9-11 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 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 rejection for new matter.
The claims quantifying mRNA expression “of any ZNF71 isoforms” and quantifying protein expression “of any ZNF71 isoforms.” No basis in the specification was identified regarding this limitation, and none of the portions of the disclosure pointed to in the remarks filed with the amendment mention ZNF71 isoforms. This claim limitation would encompass a method where an individual isoform detected specifically within a method for prognosing non-small cell lung cancer, and there is no suggestion of such a method in the disclosure. There is no suggestion that any one isoform is prognostic of NSCLC.
Furthermore, the claims recite AQUA analysis in “frozen” tumor samples, but the disclosure does not teach AQUA analysis in frozen tumor samples. While the specification mentions snap-frozen samples (p. 12-13) used to develop the 7-gene assay in PCT/US2019/036953, the specification does not provide written description for AQUA analysis using frozen tumor 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.
Claims 9-11 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.
Claims 9-11 recite in the preamble that the method a method “of providing treatment” for a patient having lung cancer, however the body of the does not mention providing treatment of any kind. Therefore, it is unclear how the preamble of the claim is accomplished by practicing the steps recited in the claim.
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 9-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed an abstract idea and a natural phenomenon. The claim(s) recite(s) determining a prognosis of said patient from the quantified protein expression of ZNF71. This step is a mental process judicial exception since it could be practiced in the mind and also a recitation of a naturally occurring correlation since the relationship between ZNF71 and prognosis of an NSCLC patient exists without any action by man. The claims further recite “automated quantitative analysis correlated with the quantified mRNA expression of ZNF71” which is also a natural law statement of a relationship that exists without any action by man. Finally claim 11 recites a further mental process judicial exception of “combining” two types of data. These judicial exceptions are not integrated into a practical application because the steps in addition to the judicial exceptions do not use of apply the judicial exceptions in any way. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the judicial exceptions are mere data gathering steps recited at an extremely high level of generality employing techniques that were well known before the filing of the instant application. See Votavova et al., Kratz et al. Guo et al., and Camp et al. See also spec p. 12 teaching AQUA is “a technique known by those skilled in the art.”
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.
Claim(s) 9 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (EBioMedicine 32(2018)102-110), cited in the IDS, in view of Kratz et al. (Lancet, 2012, p. 823-832; Cited in IDS).
Guo et al. teaches a method which includes extracting total RNA from a formalin fixed and paraffin embedded tumor of a NSCLC patient after surgical resection, generating cDNA, and quantifying mRNA expression of ZNF71 (section 2.2-2.5; Table 2).
Guo et al. further teaches measuring protein expression of ZNF71 in a formalin fixed and paraffin embedded tumor of a NSCLC of a patient after surgical resection, quantifying the expression using AQUA (section 3.2).
Claim 9 recites “quantifying …with… (AQUA) correlated with the quantified mRNA expression of ZNF71…”. This limitation requires quantifying the protein expression with AQUA, and sets forth that it is correlated with mRNA. The correlation language in the claim does not require any further or different action on the part of the practitioner (i.e. there is no method step recited) and thus, the correlation is inherent. Furthermore, since the claim is recited for the detection of mRNA and protein expression in a single sample the two points are necessarily related to one another.
Guo et al. teach that the quantified protein expression of the ZNF71 is prognostic of NSCLC outcome (section 3.2). Regarding claim 10, Guo et al. teach higher protein expression of ZNF71 is significantly associated with better patient survival, which is concordant with its mRNA results (Section 3.2).
Guo et al. do not teach extracting total RNA from a formalin fixed and paraffin embedded tumor of a non-small cell lung cancer patient after surgical resection.
Guo et al. teaches that qRT-PCR requires only a small sample and can be modified to quantify gene expression in formalin-fixed paraffin embedded tissues.
Kratz teaches that preparation and analysis of RNA from formalin-fixed paraffin-embedded tumor section followed by qRT-PCR of marker genes (p. 826). Katz teaches that the need to use snap-frozen tissue makes assays difficult in practical clinical settings, and teaches instead a method for measuring gene expression in FFPE tumor sections (p. 823).
It would have been prima facie obvious to have modified the method taught by Guo so as to have substituted FFPE tissue as taught by Kratz for snap frozen tissue for the extraction of RNA and measuring of the prognostic biomarker ZNF71. One would have been motivated to do so by the direct suggestion of Guo et al. that qRT-PCR can be modified to quantify gene expression in formalin-fixed paraffin embedded tissues and the teachings of Kratz exemplifying such a modification of qRT-PCR.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Guo in view of Kratz as applied to claims 9-10 above, and further in view of Hao (Tumor Biol. (2015) 36:1811-1817).
The teachings of Guo in view of Kratz are incorporated here. The reference do not teach combining protein expression with any of the factors recited in claim 11 for determining prognosis.
Hao et al. teach that that protein expression of POMC was associated with prognosis in NSCLC patients, and that when the protein expression and stage were used together the predictive ability of the model had a higher ROC than the protein alone. (p. 1813, 2nd column).
It would have been prima facie obvious to have modified the method of Guo in view of Kratz so as to have determined prognosis by combining the quantified ZNF71 protein expression with cancer stage in order to provide a model considered more thoroughly the totality of the data. This would have been obvious because Hao et al. showed that including stage in a model with protein expression increased the predictive ability of the prognostic model.
Double Patenting
Claims 9-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 5-10 of copending Application No. 17251359 in view of Guo and Kratz.
The copending claims teach the method of claim 9, except that the copending claims do not teach that the resected tumor samples are FFPE samples.
Guo and Kratz suggest the use of FFPE samples, as discussed previously and fully incorporated here.
It would have been prima facie obvious to have modified the method taught by Guo so as to have sampled FFPE tissue as taught by Kratz extraction of RNA and measuring of the prognostic biomarker ZNF71, and for the measuring of ZNF71 protein. One would have been motivated to do so by the direct suggestion of Guo et al. that qRT-PCR can be modified to quantify gene expression in formalin-fixed paraffin embedded tissues and can be used to quantify ZNF71 and the teachings of Kratz exemplifying such a modification of qRT-PCR.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Votavova et al. (Diagn. Mol. Pathol, 2009. 18(3): p. 176-182; cited in IDS) teach an optimized protocol for gene expression analysis of formalin-fixed paraffin-embedded tissue using real-time quantitative PCR.
US 2009/0062144 teach ZNF71 as an mRNA prognostic marker in lung cancer, see Table 1, Table 4 and Table 5.
Ye et al. Int. J. Mol. Sci. 2021, 22, 3752 teaches that the ZNF71 KRAB isoform and the ZNF1 KRAB-less isoform have different prognostic potential (see abstract).
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/ Primary Examiner, Art Unit 1682