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 reply to the previous Office action, dated August 14, 2026, has been received. By way of this submission, Applicant has amended the specification and claims 14, 16, and 18, and introduced new claims 30-33.
Claims 14-33 are pending in the application. Claims 19-24 and 27-29 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed December 31, 2025.
Claims 14-18, 25-26, and 30-33 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated May 14, 2026.
Specification
The specification was previously objected due to due to the presence of browser-executable code.
Applicant's amendment to the specification has addressed this issue, and this objection is hereby withdrawn.
Claim Objections
Claim 17 is objected to because of the following informalities: Claim 17 is objected to due to the recitation of the term "CDS+ T lymphocytes". This appears to be a typographical error; it is assumed that the correct term is CD8+ lymphocytes, as recited in the previous claim set. Appropriate correction is required.
Response to Arguments
Applicant argues that Regev does not teach every aspect of the claims as amended; specifically, Regev does not teach the specific treatment selections recited in amended claim 14 and 18.
Applicant's amendments to the claims have addressed this issue, and the rejection under 35 U.S.C. 102 to Regev is hereby withdrawn.
Applicant argues that the amended claims do not merely observe or report a natural correlation but instead incorporates this natural correlation into a practical application by using the information to inform a specific treatment method. Additionally, the claim recites a specific immunohistochemical pathology process and defined scoring as part of the "evaluating" step, which does not preempt other uses of the alleged judicial exception, and the determination of a SQSTM1/p62-high or SQSTM1/p62-low classification based on the defined staining scores cannot be considered to be routine or conventional in the art at the time of the filing.
Claims 16-17, and 32 do not require any particular treatment, and the use of immunohistochemistry was known at the time to be routine and conventional in the art of detecting biomarkers in a cancer sample (see, e.g., Regev (US20200157633A1), cited previously, and Schlafli (Eur J Histochem. 2015 May 5;59(2):2481). The use of antibodies or immunoassays to determine levels of a biomarker has been characterized by the Court as "mere data gathering" and "insignificant extra-solution activity". Determining the level of a biomarker has been recognized by the courts as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). MPEP 2106.05 (II). Using this method to make such a diagnosis would have been a routine, conventional choice, and as such does not offer significantly more than the exception itself.
The rejection under 35 U.S.C. 101 to claims 14-15, 18 and 25-26 is hereby withdrawn, the rejection to claim 16-17 is maintained and extended to include new claim 32.
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 16-17 and 32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claims recite a law of nature, a natural phenomenon, or an abstract idea. This judicial exception is not integrated into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012). "[L]aws of nature, natural phenomena, and abstract ideas" are not patentable. Diamond v. Diehr, 450 U.S. 175, 192 n.14, 209 USPQ 1, 10 n. 14 (1981); see also Bilski v. Kappos, 561 U.S. 593, 604, 95 USPQ2d 1001, 1007 (2010). "Phenomena 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, 70, 175 USPQ 673, 676 (1972). 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." See, e.g., Gottschalk at 71–72. Essentially, appending conventional steps, specified at a high level of generality, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, phenomena, and ideas patent-eligible.
In Prometheus, the Court found that "[i]f a law of nature is not patentable, the 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." Additionally, "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". Parker v. Flook, 437 U.S. 584, 588-89, 198 USPQ 193, 196 (1978); see also Bilski: "[T]he prohibition against patenting abstract ideas 'cannot be circumvented by' . . . adding 'insignificant post-solution activity'" (quoting Diehr, 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."
The first step under this guidance is determining if the claim is directed to one of the four statutory categories (process, machine, manufacture, or composition of matter). In this case, the claims are a method (process). The second step is determining if the claims recite or involve judicial exception(s), such as laws of nature, natural phenomena, natural products, or an abstract idea. In this case, the claims are drawn to methods for predicting in vitro the resistance of a tumor to a therapy and for predicting the survival rate of a patient afflicted by a tumor, comprising evaluating the presence or the absence or the amount of an SQSTM1/p62 protein in a biological sample originating from the tumor and drawing a conclusion based upon the levels of SQSTM1/p62 detected as they relate to immune checkpoint inhibitor therapy. This is a natural correlation/observation of a natural phenomenon, the correlation between levels of SQSTM1/p62 resistance to therapy with an immune checkpoint inhibitor, which is a judicial exception.
Furthermore, the judicial exceptions are not integrated into a practical application, as the claims do not rely on or use the exceptions in a further step. See MPEP 2106.04(d). Thus, it must be determined if the claim as a whole recites something significantly more than the judicial exceptions.
The methods recite a step of evaluating the presence or the absence or the amount of an SQSTM1/p62 protein in a biological sample by detecting the SQSTM1/p62 protein in tumor cells of a tissue biopsy by immunohistochemistry using an anti-SQSTM1/p62 antibody. This is well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality), as evidenced by Applicant's specification at page 6, lines 9-13 and 30-34. Additionally, Regev (US20200157633A1, cited previously), and Schlafli (Eur J Histochem. 2015 May 5;59(2):2481) also teach the use of immunohistochemistry to identify this biomarker. Also see Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). Using known methods disclosed in the specification such as immunohistochemistry, immunoblotting, immunofluorescence in situ, or flow cytometry to detect a protein in a sample would have been a routine, conventional choice, and as such does not offer significantly more than the exception itself.
The claimed method does not affect any treatment step, or any steps at all beyond abstract ideas and observation of a natural phenomenon, and well-known, conventional methods to perform said observation.
The remaining claims further characterize the exception itself, e.g., additional details for the sample or patient, and do not add significantly more.
Therefore, claims 16-17 and 32 are patent ineligible.
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 14-18, 25-26 and 30-33 are rejected under 35 U.S.C. 103 as being unpatentable over Regev (US20200157633A1) in view of Schlafli (Eur J Histochem. 2015 May 5;59(2):2481), Soliman (Onco Targets Ther. 2016 Dec 21:10:101-112), and Fournel (Cancer Lett. 2019 Nov 1:464:5-14). This is a new grounds of rejection, necessitated by Applicant’s amendments to the claims.
Regev teaches a method for predicting response to checkpoint blockade therapy by identifying a gene signature (para. 0008). Regev further teaches methods of detecting immune checkpoint inhibitor resistance, comprising detecting the expression or activity of an SQSTM1 polypeptide, wherein low levels of gene expression are correlated with higher levels of immune checkpoint inhibitor resistance (para. 0010-0011, also see para. 0080 and Figure 12).
Regev also teaches that gene expression may be compared to a control (para. 0071).
Regev further teaches that gene expression may be evaluated by immunohistochemistry (para. 0150).
Regev further teaches that this method may be performed in situ (para. 0150, 0499, and 0009), which is pertinent to claim 15.
Regev further teaches that detection of immune checkpoint inhibitor resistance is useful in predicting rates of survival (para. 0430), which is pertinent to claim 16. Regev also teaches that detecting an immune checkpoint inhibitor resistance signature indicates a 10-year survival rate of less than 40%, and not detecting the signature indicates a 10-year survival rate of greater than 60% (para. 0021).
Regev further teaches evaluation of levels of CD8+ T lymphocytes (para. 0497) and PD-L1 (para. 0506), which is pertinent to claim 17.
Regev further teaches that this method may be performed on a tissue biopsy (para. 0405 and 050), which is pertinent to claim 26.
While Regev does not teach SEQ ID NO: 1, Applicant's specification at page 4 states that SEQ ID NO: 1 is the human SQSTM1 protein sequence. As Regev teaches human SQSTM1, Regev inherently teaches SEQ ID NO: 1.
However, Regev does not teach evaluating cytoplasmic and dot-like staining intensity, or combinations of checkpoint inhibition and paclitaxel or cisplatin.
Schlafli teaches detecting levels of p62 by immunohistochemistry on a tumor sample and evaluating cytoplasmic and dot-like staining intensity by comparison to a control tissue sample (Figure 3).
Schlafli further teaches that a score of 3 indicates strong staining (Table 1 and page 176, left column).
Soliman teaches that treatment with chemotherapy enhances treatment with immune checkpoint inhibitors in patients that are resistant to treatment with immune checkpoint inhibitors alone (page 103: "Chemotherapy in combination with checkpoint inhibitors").
Soliman further teaches combinations of paclitaxel and an immune checkpoint inhibitor (page 106).
Fournel teaches combinations of cisplatin and immune checkpoint inhibitors to treat cancer (abstract).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Regev, Schlafli, Soliman, and Fournel to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since Regev, Schlafli, Soliman, and Fournel are all concerned with evaluation of biomarkers for cancer or treatments with immune checkpoint inhibitors. Methods of evaluating a sample by immunohistochemistry for SQSTM1/p62 were known in the art by Regev and Schlafli, and the correlation between low levels of SQSTM1 and higher levels of immune checkpoint inhibitor resistance are also taught by Regev. The combination treatment of Soliman suggests one such method to overcome this known resistance. Other combination treatments for cancer, such as cisplatin and immune checkpoint inhibitors were also known in the art, according to Fournel. One of ordinary skill could evaluate levels of SQSTM1 in a tumor sample by the methods of Regev and Schlafli and then use this information to select an appropriate treatment by following the teachings of Soliman and Fournel. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 6:00 to 2:00.
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/PETER JOHANSEN/Primary Examiner, Art Unit 1642
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