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 I, claims 1-16, 18, 20, and newly added claims 38 and 39 in the reply filed on 6/18/2026 is acknowledged. The species election requirements are withdrawn and all species are rejoined.
Claims 1-16, 18, 20, and newly added claims 38 and 39 are pending and under consideration in this office action.
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 1-14 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 mapping the border of a melanoma tumor by detecting expression of S100A8 and/or S100A9. However this is a natural correlation between the expression levels of the recited biomarkers and melanoma tumors. 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 “mapping” a border, and “identifying” a border of a tumor by comparing expression levels in different sample regions. This is a recitation of abstract ideas because they encompasses recognizing patterns and drawing conclusions which can occur entirely within the mind. It is therefore determined that the claims recite 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 applying an adhesive patch to a skin area overlaying a tumor region and an area of skin not overlaying the melanoma tumor, removing the adhesive patch, and determining gene expression of the biomarkers on the sample obtained from the patch. 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. Adhesive patches for obtaining skin samples for molecular analysis were available well before the effective filing date of the instant invention (see specification page 10).
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 step of obtaining a sample using an adhesive patch is well understood, routine, and conventional in the field, as exemplified by the references in this office action as well as the references cited in the specification. Additionally, the steps of detecting expression levels are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, 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 § 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 1-6, 8-16, 18, 20 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Lezcano (Lezcano et la; Am J Surg Pathol, 2018; vol 42, pages 1456-1465) in view of Chang (Chang, S.H.; US2019/0367994; cited in the IDS filed 2/5/2024), (Riker et al; US2008/0113360; cited in the IDS filed 2/5/2024), and Clarke (Clarke et al; Journal of Cutaneous Pathology; 2015, vol 42, pages 244-252).
With regard to claims 1-6, 15, 16, 18, and 20, Lezcano teaches differential RNA expression of PRAME has been used to detect melanoma tumors. Lezcano teaches a method of detecting melanocytic tumors using PRAME protein expression (antibodies linked to an imaging agent) (see abstract; whole document). Lezcano teaches that PRAME expression was able to identify melanoma tumor tissue, and was generally absent in normal tissue (see whole document; figure 5; pages 1457, 1462). Lezcano teaches that expression analysis was able to differentiate melanoma in situ from adjacent benign skin (see page 1457; figure 5) and that it will likely be useful in the evaluation of margin status (pages 1457, 1462). Lezcano teaches that biological samples were excised, but does not teach using an adhesive patch to obtain a biological sample. However, Chang teaches a method of distinguishing melanoma from dysplastic nevi or normal skin by applying an adhesive patch (tape stripping) to a skin area of the subject, removing the skin patch to obtain a sample, and analyzing the skin sample for protein or nucleic acid biomarkers (see whole document; para 0014, 0068, 0142). Chang teaches treating melanoma using surgical excision (para 0004). Chang teaches nucleic acid analysis techniques for evaluating gene expression includes quantitative PCR and microarrays (see para 0074-0101). Chang teaches applying the adhesive patch to different skin lesions as well as adjacent normal skin (para 0009-0016). Chang teaches tape stripping holds promise for diagnoses and prognosis because in melanomas, the pigmented cells migrate into the epidermis and that there are changes in the dermis and epidermis adjacent to melanoma. Chang teaches this area is expected to be sampled with tape stripping (para 0065). Additionally, Chang teaches that for tape stripping of pigmented lesions, the lesions should be smaller than that of the tape disk and that the area of the tape that touches the lesion should be “generously demarcated” on the tape with an insoluble ink pen so that this area may be cut away from the surrounding tape by the laboratory as part of biomarker extraction (para 0136). Therefore, and with regard to instant claim 11, Chang teaches that the tape strip comprises at least a portion of skin surface overlaying the melanoma tumor and a portion of the skin that does not. Although Chang does not expressly state the purpose of the method is to map the border of the melanoma tumor, Chang does suggest doing so. Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have used tape stripping, as taught by Chang, in the method of detecting and differentiating melanoma tumor from normal skin tissue, including the evaluation of the margin of melanoma tumors, using biomarker analysis as taught by Lezcano. The ordinary artisan would have been motivated to use the less invasive method of tape stripping taught by Chang in the method of Lezcano, and to have surgically excised any melanoma found, as taught by Chang. Additionally, since Lezcano teaches that tumor margins could be differentiated by biomarker analysis and Chang teaches separate analysis of tape strip portions overlaying the tumor border from normal skin, the ordinary artisan would have had a reasonable expectation of success in applying the method of Chang to determine tumor margins, thereby mapping the border of a melanoma tumor, as taught by Lezcano.
With regard to claims 1-6, 15, 16, 18, and 20, Lezcano in view of Chang do not teach biomarker analysis comprises detecting RNA or protein expression of S100A8 and/or S100A9, however Riker teaches the differential expression of biomarkers, including S100A8 and S100A9, in melanoma compared to nonmalignant tissue (see whole document; para 0007; para 0038; table A). Riker teaches analysis of both RNA and protein biomarkers for detection of melanoma. Additionally, Clarke teaches a gene expression signature that differentiates benign nevi from malignant melanoma which includes PRAME, S100A8, and S100A9 (see whole document; pages 247-248; table 2). Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date, to have included biomarker analysis of S100A8 and S100A9 in the method of Lezcano and Chang, because Riker and Clarke teach that differential expression of these biomarkers was able to differentiate malignant melanoma from benign skin.
Regarding claims 8-10 and 39, Riker, Clarke and Lezcano each teach comparison of expression to a threshold. Therefore, it would have been prima facie obvious to have established a predetermined threshold, either expressed as an amount or percentage, so as to have a point of comparison to determine if the biomarker expression of a skin region was above or below the threshold so as to classify the area as tumor or benign/normal.
Regarding claims 12 and 13, Chang teaches sampling skin areas suspected of a pathological state and the surrounding skin (para [0046] - "Samples for the present invention typically are taken from a skin lesion, which is suspected of being the result of a disease or a pathological or physiological state… or the surrounding margin or tissue. As used herein, "surrounding margin" or "surrounding tissue" refers to tissue of the subject that is adjacent to the skin lesion, but otherwise appears to be normal or free from lesion"). Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date to sample different skin areas, including those that comprise at least 50% of the skin surface overlying the melanoma tumor, as well as those with less than 50% of the suspected melanoma tumor for the obvious benefit of determining the margins of the malignant tissue.
Regarding claim 14, Chang teaches at para [0138] - "Apply the tape to the skin site. If more than one tape is used, apply tapes in sequential order starting from the left side. Use a surgical skin marker and/or a water soluble marker to mark the location of the tape on the skin in order to align subsequent tapes" and at para [0139] "Using a marking pen, demarcate a zone around the lesion such that the area of the lesion is encompassed within the inked boundary and the boundary is approximately 1 mm from the lesion border". It is additionally noted that Riker, Clarke, and Lezcano teach analysis of different skin areas to differentiate normal/benign skin from melanoma. Therefore, it would have been immediately obvious to the ordinary artisan to use more than one skin patch, in different border areas, so to assess the margins of the entire tumor, particularly if it is larger than the tape strip.
Claims 7 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Lezcano (Lezcano et al; Am J Surg Pathol, 2018; vol 42, pages 1456-1465) in view of Chang (Chang, S.H.; US2019/0367994; cited in the IDS filed 2/5/2024), (Riker et al; US2008/0113360; cited in the IDS filed 2/5/2024), and Clarke (Clarke et al; Journal of Cutaneous Pathology; 2015, vol 42, pages 244-252) as applied to claims 1-6, 8-16, 18, 20, and 39 above, and further in view of Gilbert (US 2012/0172685; cited in the IDS) and Zinreich (Zinreich et al; US 5,306,271).
The teachings of Lezcano, Chang, Clark, and Riker are set forth above. Although Chang teaches to use insoluble ink to demarcate the border of the lesion, Lezcano, Chang, Clark, and Riker do not teach an adhesive patch that comprises registration marks which transfers indicia of registration marks when applied to the skin, and correlating the transferred indicia to the registration marks. However, the art teaches adhesive patches that mark the skin with indicia of registration marks. For example, Zinreich teaches transferring skin markings for radiation therapy using an adhesive surface that release markings onto a patient’s skin area (see whole document). Additionally, Gilbert teaches an adhesive patch (para 0211) which transfers markings onto skin. Therefore it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have included the use of adhesive patches that transferred markings on to the skin, as taught by Zinreich and Gilbert, in the method of Lezcano, Chang, Clark, and Riker, for the obvious benefit of identifying regions of skin that had been screened for melanoma and to distinguish the different regions so as to differentiate normal regions from that that directed to tumor samples.
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 can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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, Winston Shen, can be reached at (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEHANNE S SITTON/ Primary Examiner, Art Unit 1682
