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 III and the species of ZIC4 and cg211227068 in the reply filed on 11/14/2025 is acknowledged. It is noted that cg numbers are not required by Claim 21 and as such the species is interpreted as ZIC4.
Claims 1-14, 18-19 and 21 are pending. Claims 15-17, 20 and 22-98 have been cancelled.
Claims 1-14, 18-19 are withdrawn as being drawn to a nonelection.
An action on the merits for claim 21 is set forth below.
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 21 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 21 is indefinite. The claim recites “optionally treating…..” it is not clear if this optional language is intending to limit so that only one or more of ai-av is determined or if the entirety is optional. Furhtermore it is not clear based upon the election is the claims are intending to perform ai-av or based upon the “or” language in the preamble if the claims can encompasses only one of subsets. As the election was only one gene that is in aiv or av, it is interpreted that one embodiment is the measurement on only one subset.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 21 rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of one or more of the genes in each of ai-av listed is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The recited alternative species in the groups set forth here do not share a single structural similarity, as each method relies on detection of different biomarker position. Each biomarker that could be detected is itself located in a separate region of the genome and has its own structure. The nature of genes is that they are differences within a population. The only structural similarity present is that all detected positions are part the nucleic acid structure. The fact that the markers comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with treatment. For example, the biomarker APC has a distinct chemical structure as compared to, for example, ZIC4 since the gene can only be understood within the context of the nucleotides, which are structurally dissimilar. Accordingly, while the different markers are asserted to have the property of being indicative of treatment, they do not share a single structural similarity. Nor is the functionality is clear from the very nature of the biomarkers.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 21 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation without significantly more. The claim(s) recite(s) a judicial exception of correlation of diagnosis and CpG methylation expression. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not integrate the judicial exception to steps that are not considered routine and conventional steps.
These judicial exceptions are not integrated into a practical application because the claims only recite the natural correlation and routine and convention steps, wherein the routine and convention steps does not integrate the judicial expectation. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps are considered general and routine knowledge in the prior art as exemplified by the prior (as discussed below).
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, a natural phenomenon
The correlation of methaytlion CpG data and diagnosis is considered a natural correlation. The step of providing determining the methylation expression in the sample are considered a routine and conventional step as detailed below.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as the steps require only routine and convention steps and does not integrate the judicial exception to a practical application.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No as the claims do not require any elements that integrate the judicial exception. Feber et al. (US Patent Application 2018/0305765).teaches a method of measuring levels of methylation by CpG detection in ZIC4 promoter using cfDNA from a blood sample (paragraph 38 and table 1).
These methods are considered generic recitations of general methods of methylation determination that do not overcome the rejection.
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) 21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Feber et al. (US Patent Application 2018/0305765).
With regard to claim 21, Feber et al. teaches a method of measuring levels of methylation by CpG detection in ZIC4 promoter using cfDNA from a blood sample (paragraph 38 and table 1). With regard to the wherein clause of claim 21, this wherein is limited to when there is increased levels detected. As such one embodiment is levels are not increased and the wherein clause is optional. Further with regard to the diagnosis preamble, the diagnosis of the diseases are based upon a detection of the increased level, therefore the positive active steps are not limited. It is noted that the treatment step is optional.
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.
Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pfeifer et al. (US Patent Application Publication 20090305256 December 10, 2009) in view of Lo et al. (US patent Application Publication 2019/0241979 August 8, 2019).
With regard to claim 21, Pfeifer et al. teaches diagnosis of lung squamosas cell carcinoma by detection of increased methaytlion of CpG sites in the promoter of ZIC4 (para 57-58 and table 2). It is noted that the treatment step is optional.
However Pfeifer et al. does not teach of cfDNA from blood.
With regard to claim 21, Lo et al teaches screening of cfDNA derived from blood samples from adenocarcinoma lung patients to measure levels of methylation (para 333,466,557). Lo et al. teaches that this screening includes probes on the Illumina Infinium Human Methylation 450K bead chip array (para 557). As indicated by the specification ZIC4 used in the specification is the probe cg21127068 on this bead chip array.
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Pfeifer et al. to screen other known sample types such as the one taught by Lo et al. to make determinations on expression of Zin4 methylation. The ordinary artisan would be motivated to use cfDNA as taught by Lo et al. because Lo teaches that this gene is on known arrays for methylation detection and the obtaining cfDNA is non-invasive as compared to the tissue isolation of Pfeifer et al.
Conclusion
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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/KATHERINE D SALMON/ Primary Examiner, Art Unit 1682