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 II, species SEQ ID NOS 1, 2, 4, and 5 in the reply filed on 10/3/2025 is acknowledged.
Claims 37, 38, and 41 are withdrawn from consideration as being directed to non-elected species.
An action on the merits of claims 24-30, 33-36, 39, 40, and 42-45 is set forth herein.
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 24-30, 33-36, 39, 40, and 42-45 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites a method of detecting lung cancer “based” on the methylation levels of HOXB4 and SRCIN1. However, this recitation is a natural correlation between methylation levels of the recited genes and lung cancer. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites “comparing methylation levels” and “detecting the lung cancer” which are recitations of abstract ideas because they encompasses conclusions and determinations which can occur entirely within the mind. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of detecting methylation levels of the recited genes, however this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method. With regard to claims 33-36, 39, 40, and 42-45, although the claims recite SEQ ID NOS, the claims broadly encompass any primers or probes for detecting methylation within the recited genes due to the recitation of between 85% to 99% identity as well as the recitation of “nucleotides shown in”. Even claims which do not recite % identity do not require a primer or probe “comprising” the entire SEQ ID NO: because the recitation of “shown in” encompasses any number of nucltoides within the recited SEQ ID Nos. Additionally, although claim 25 recites “administering an anti-lung cancer drug”, this is a generally recited element which is considered nothing more than instructions to apply the law of nature because no particular treatment is required. As such, the “administering” step is merely a generalized “treat” limitation with no particularity that integrates the judicial exception into a practical application. The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words "apply it.” CLS BankInt’l, 134 S.Ct. at 2358; Prometheus, 132 S. Cl, at 1294.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the sample limitations are considered insignificant post solution activity. The steps of detecting methylation levels, even with the recitation of particular SEQ ID NOS, do not provide any particular reagents (see reasons set forth above for claim interpretation of % identity and “shown in”) that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. Therefore these steps/elements are not only mere data gathering, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
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.
Claims 24-30, 33-36, 39, 40, and 42-45 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
The claims recite “detecting the lung cancer based on a deviation of the methylation levels of the sample and the normal control sample”, however the recitation of “based on” is vague. The relationship between the methylation levels and diagnosis is not made clear by the recitation of “based on”.
Claims 33 and 34 recite “wherein said detecting methylation levels of … is by a gene methylation detection kit comprising … a gene methylation detection kit…”. However, the claims do not set forth any active steps, such that it is not clear how the components of the kits are used in the method. The claims simply recites elements pertaining to the structural components of the kit rather than active method steps.
The claims recite vague structural elements with regard to the primers, probes, and kits in claims 33, 34, and the claims that depend from them. The claims are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors. For example, the recitation of “a first forward primer comprising a nucleotide sequence having an identity… to any one of nucleotide sequences shown in SEQ ID NOS 1…” appears to encompass a primer that comprises any sequence, with less than 100% identity, from within any of the recited SEQ ID NOS. It is not clear if this is the intention or the result of translation from a foreign document. The same analysis holds for the remainder of the limitations pertaining to primers or probes in these claims and the claims that depend from them. It should be noted that the recitation of “a nucleotide sequence” and “shown in” in claims 35, 36, 39, 40, and 42-45 appears to be directed to any nucleotide within the recited SEQ ID NOS, rather than all of the nucleotides of the SEQ ID NO:. Accordingly, the metes and bounds of the primers and/or probes required by the claimed methods is unclear.
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.
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.
Claims 24-25, and 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Daugaard (Daugaard et al; Scientific Reports, DOI: 10.1038/srep35807, pages 1-11, 2016) and Salhia (Salhia, Bodour; WO2019/035100).
Daugaard teaches methods of detecting lung adenocarcinoma (claims 29 and 30) by detecting methylation of a number of CpG islands including HOXB4 (see abstract). Daugaard teaches measuring and comparing CpG methylation levels in tumor and normal lung tissue (claim 27), and detecting deviation in methylation levels between the samples. With regard to claim 28, Although Daugaard does not teach samples such as alveoli lavage fluid, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have detected methylation levels in alveoli lavage because it is less invasive than tumor biopsy.
Daugaard does not teach detecting methylation levels of SRCIN1, or administering an anti-lung cancer drug, however Salhia teaches measuring methylation levels of a number of genes, including SRCIN1, for cancer detection, including lung cancer (see pages 65-110). Salhia also teaches treating a subject having cancer (para 0107). Therefore, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date, to have included the genes taught by Salhia in the methylation detection method of Daugaard for the benefit of analyzing a more comprehensive panel of genes differentially methylated in lung cancer. With regard to claim 25, it would have further been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have treated lung cancer in patients taught by Daugaard, by administering an anti-lung cancer drug for the obvious benefit of treating the disease as taught by Salhia.
Claims 26, 33-36, 39, 40, and 42-25 are rejected under 35 U.S.C. 103 as being unpatentable over Daugaard and Salhia as applied to claims 24, 25, and 27-30 above, and further in view of Fackler (Fackler et al; Cancer Research, vol 64, pages 4442-4452, 2004).
The teachings of Daugaard and Salhia are set forth above. Daugaard and Salhia do not teach detecting methylation levels using quantitative methylation specific PCR, however Fackler teaches the successful analysis and measurement of CpG methylation in a number of genes from a single sample (see abstract, discussion). Fackler teaches designing primers and probes for the accurate measurement of CpG methylation levels (see page 4443-4444). Therefore, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date, to have using the quantitative methylation specific PCR method taught by Fackler, to analyze and measure the methylation levels of the genetic regions taught by Daugaard and Salhia because Fackler teaches the method can be used to accurately measure CpG hypermethylation in genes diagnostic of cancer. With regard to claims 33-36, 39, 40, and 42-45, Daugaard and Salhia teach sequences and the location of CpG sites for analysis. Although the claims recite particular SEQ ID NOS, the scope of the primers and probes encompassed by the claims appears to be much broader, as outlined in the rejection under 35 USC 112(b) set forth above. Accordingly, absent secondary considerations, the broad scope of the possible primers and probes for methylation detection of HOXB4 and SRCIN1 encompassed by the claims are considered obvious over the teachings of the cited prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Winston Shen, can be reached on (571) 272-3157. The fax phone number for organization where this application or proceeding is assigned is (571) 273-8300.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682