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 with traverse Group I and specific combination of biomarkers of ZNF677, FBN2, PCDH8, TFAP2B, TAC1, FLRT2, ADAMTS19, BMP7 and SIM1 in the reply filed on 2/06/2026 is acknowledged. The traversal is on the ground(s) that methylation status of biomarkers is not distinct from primers and probes, however, the claims have been amended to require claim back to the independent claims (p. 2). This arguetmsn has been reviewed but is not persuasive as primers and probes and the kit are structures which have been restricted from group I as there is no single general inventive concept. The arguetmsn that one would need to use primers and probes is not an arguetmsn to rejoin these methods and structures in light of the art of record. Further it is noted that even though the claims have been amended, the claims 11-15 are still drawn to a product and the amendment appears to be limiting the intended use and not dependency.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-17 are pending.
Claims 5-17 have been withdrawn as being drawn to a nonelected invention.
An action on the merits for claims 1-4 is set forth below.
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. See page 1,17,18.
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 1-4 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for determining DNA methylation level, does not reasonably provide enablement for identification of ccRCC. 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 or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The breadth of the claims and nature of the invention
The claims are drawn for identification of ccRCC in patients diagnosed with ccRCC or suspected of having ccRCC consisting of obtaining a biological sample, determining the methylation status of ZNF677, FBN2, PCDH8, TFAP2B, TAC1, FLRT2, ADAMS19, BMP7, and SINM1, or fragments, identifying samples as having ccRCC when DNA methylation is observed.
However, the specification has not provided any guidance for any identification of ccRCC based upon any level of methylation, whereas, the art, as discussed below, teaches that expression level in samples types from various species are not directly correlative.
Nature of the Invention
The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
Guidance in the Specification and Working Examples
The specification provides patients diagnosed with ccRCC were sampled for tissues (p. 15).The specification teaches that urine samples was detected (p. 16). The specification provides determining methylation statues of the recited biomarkers (p. 25-26). The specification teaches measuring overall methylation level differences (p. 29). The specification provides data of diagnosing ccRCC cases in urine (p. 35) however, the specification does not provide the breadth of the claims rather a particular sample and particular methylation levels (p. 36). Although there are correlations provided the specification does not provide that the combination of biomarkers in any samples from any species would predictive of identification of ccRCC. Furthermore, the term “identification of ccRCC” encompasses a number of phenotypes including diagnosing, predisposition to ccRCC, aggressive ccRCC, predisposition to aggressive ccRCC, staging of ccRCC. The specification has not provided guidance for such correlations.
As such the experiments provided by the instant specification provide a scope of enablement; however, they do not provide guidance the breadth of the correlations. Whereas the art, provided below, teaches that each of these factors have different expression of genes.
The unpredictability of the art, the state of the prior art
In the instant case it is unpredictable as to whether the results obtained in human individuals could be extrapolated to non-human individuals. Knowledge that particular gene is hypermethylated in one organism (i.e. humans) does not allow one to conclude that loci will also be hypermethylated in other organisms and will be associated with an abnormal condition. In particular Feng (PNAS 2010 Vol 107 No 19 pages 8689-8694) teaches that although DNA methylation likely has a conserved role in gene silencing, the levels and patterns of DNA methylation appear to vary drastically among different organisms (abstract). As such it is unpredictable as to whether methylation levels in one species would be predictive of monitoring or assisting in treatment selection in any other species.
Quantity of Experimentation and Conclusion
The quantity of experimentation in this area is extremely large as it requires the analysis methylation expression level of these biomarkers in any sample from any species and correlations to a myriad of different phenotypes encompassed by “identification”.
As neither the art nor the specification provides guidance as to the breadth of these associations, the claims require trial and error experimentation, with the outcome of each analysis being unpredictable. The skilled artisan would have to test each sample type in each species for correlation to each of the encompassed correlations. This correlation would take many intervening steps without providing any guarantee of success.
The specification does not provide clear guidance for the breadth of the claims, and the art teaches that these types of associations are unpredictable.
Thus given the broad claims in an art whose nature is unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, and the negative teachings in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the methods of the claims as broadly written.
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 1-4 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 1-4 are indefinite over “identification of ccRCC”. This phrase is unclear it is not clear the metes and bounds of the term. It is not clear if the claim is intending for diagnosing ccRCC or identifying the type of ccRCC. As such it is not clear how to perform each of the patients in the claim. If the patient with ccRCC is used, it is not clear what the artisan would be diagnosing. However, if it is identifying the type, it is not clear how to determine a type in a patient that does not have ccRCC (e.g. suspected). Therefore the metes and bounds are unclear.
With regard to claims 1-4, the phrase “defined by…(SEQ ID ….)”. It is not clear the metes and bounds of the term. It is not clear if the “defined by” is limiting the claims to comprising, consisting of or some other fragment of the structures listed. Furhtermore, the parentheses are unclear as it is not clear if the claims should be limited to the gene name or the particular structure of the SEQ ID numbers.
Claim 2 is unclear as it is not clear the metes and bounds of the term “suspected to consist of”. It is not clear the structures required to be “suspected to consist of” the particular samples. Further, the term “preferably” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 1-3 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a natural phenomenon without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Note that the unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012).
The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010) and in Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014).
Applicant’s attention is directed to the USPTO January 7, 2019 Revised Patent Subject Matter Eligibility Guidance (i.e., “PEG”) available at URL:
<https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf>.
Regarding Step 1 of the PEG, the claims are directed to the statutory category of a process.
Regarding Step 2A, prong one, the claims recite the judicial exception of a law of nature. The claims recite relationship between analyzing methylation status and “identifying individuals having ccRCC”. As in Mayo Collaborative Services v. Prometheus, the recited relationship to the disease is a natural phenomenon that exists apart from any human action.
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). The steps of providing a sample and determining DNA methylation of a panel of biomarkers, is not considered an integration as rather, it is using any routine and conventional methods of methylation analysis. Further, the dependent steps merely limit the types of conventional assay techniques and methylation detected but do not limit the steps themselves to integrate the method and the judicial exception.
Regarding Step 2B, the next question is whether the remaining elements/steps – i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than routine and conventional activity and do not add something “significantly more” so as to render the claims patent-eligible. The additionally recited steps are routine in the prior art. The claims are using a known method of analysis of methylation. Further Liu et al. (US Patent Application 2019/0292599 September 26, 2019) teaches obtaining a sample and determining methylation (paragraph 28, 174 and table 4). Liu et al. teaches whole genome methylation and as such would encompass the regions claimed by at least a fragment of the DNA sequences.
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.
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 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. (US Patent Application 2019/0292599 September 26, 2019).
With regard to claim 1, Liu et al teaches obtaining a sample and determining methylation (paragraph 28, 174 and table 4). Liu et al. teaches whole genome methylation and as such would encompass the regions claimed by at least a fragment of the DNA sequences.
With regard to claim 2, Liu et al. teaches a sample that detects tissue or fluid (para 80).
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.
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 on 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682
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