DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election of Group I (claims 13-28) in the reply filed on August 12, 2026 is acknowledged. Applicant’s election in the response of August 12, 2026 of the following species for examination is also acknowledged: (i) STAB1; (ii) N-hydroxy-4-((5-thiophen-2-yl)-1 H-tetrazol-1-yl)methyl) benzamide (ITF3756); and (iii) melanoma.
The response does not state whether the elections are made with or without traverse. Since the response does not include anything that would constitute a traversal. That is, the response does not distinctly and specifically point out the any supposed errors in the restriction requirement. Accordingly, the election has been treated as an election without traverse per MPEP 818.01(a).
Claims 18-20 and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (claims 18-20) or a nonelected invention (claim 29), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 12, 2026.1
Priority
3. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
4. Applicant’s submission of an Information Disclosure Statement (IDS) on May 21, 2024 is acknowledged. All of the cited references have been considered.
Drawings
5. The drawings filed on May 21, 2024 are acceptable.
Specification
6. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see pages 11, 26, and 44). 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.
Specification Amendment
7. The amendment to the specification filed on May 21, 2024 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: the change of “US2012/176076” to “US2015/176076” on page 6. As discussed in MPEP 2163.07 II, correction of an obvious error is permitted only when the ordinary artisan would recognize both the existence of the error and the appropriate correction. In this case, the ordinary artisan would have recognized that “US2012/176076” is an error since the ‘076 pre-grant publication is not related to HDAC6 inhibitors or RNA biomarkers. The problem, though, is that the appropriate correction would not have been apparent since the ordinary artisan would not have immediately recognized that the publication year and not some other portion of the publication number was incorrect. Accordingly, the specification amendment introduces new matter. Applicant is required to cancel the new matter in the reply to this Office Action.
Claim Objections
8. Claim 13 is objected to because the word “the” should be inserted before “genes” in the penultimate line of step (a).
Claim 16 is objected to because each instance of “expression value” should be replaced with “expression level” to maintain consistency with claim 13.
Claim 17 is objected to because “in vitro” and “ex vivo” should not be hyphenated.
Claims 21 and 22 are objected to because it appears that an extra space is present in “H-tetrazol-1 - yl”.
Claim 28 is objected to because “non small” in line 2 should be hyphenated.
Claim Rejections - 35 USC § 101
9. 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 13-17 and 21-28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claim 13
Claim 13 is drawn to a method for “evaluating the efficacious dose and/or the biological activity of an HDAC6 inhibitor” that comprises determining the expression level of at least one RNA biomarker modulated by an HDAC6 inhibitor and comparing the determined expression level with that of a reference sample. As noted above, Applicant has elected STAB1 as the RNA biomarker and N-hydroxy-4-((5-thiophen-2-yl)-1 H-tetrazol-1-yl)methyl) benzamide (ITF3756) as the HDAC6 inhibitor for examination.
Claim 13 recites multiple judicial exceptions. First, the claim recites a correlation between the expression level of the elected RNA biomarker (STAB1) and the efficacy and/or biological activity of the elected HDAC6 inhibitor (ITF3756), which is a natural law. Second, the claim also recites multiple abstract ideas. More specifically, in step (a), “determining the expression level of at least one RNA biomarker” encompasses a mental step since the language embraces simply reading a previously measured expression level from a database or report. In other words, step (a) does not require measuring an RNA expression level using, e.g., one of the methods recited in claim 26. As well, in step (b), the recited “comparing” step encompasses a mental step and/or mathematical calculation of comparing results obtained for a patient sample with a standard control. Thus, the claims are directed to a plurality of judicial exceptions.
The judicial exceptions in claim 13 are not integrated into a practical application because the claim does not require using them in any sort of practical application (e.g., to alter treatment of a patient). Instead, the claim only recites the aforementioned judicial exceptions.
Claim 13 also does not include additional elements that are sufficient to amount to significantly more than the judicial exception because nothing is required by the claim in addition to the judicial exception. As noted above, the “determining” step encompasses a mental step and/or mathematical calculation and does not require performing any type of laboratory step (e.g., array hybridization or quantitative PCR). And, even if “determining” was construed to require a “wet lab” measurement step, the step is recited at such a high degree of generality as to be a mere instruction to apply the judicial exception.
Thus, claim 13 is rejected under 35 U.S.C. 101 as being directed to ineligible subject matter.
Claims 14, 17, 21-25, 27, and 28
Each of these claims depends directly or indirectly from claim 13.
Claim 14 depends from claim 13 and requires the efficacious dose and/or biological activity of the HDAC6 inhibitor to be evaluated during or after the therapeutic treatment of a patient affected by cancer. Claims 27 and 28 depend from claim 14 and further limit the cancer. As noted above, Applicant has elected “melanoma” as the species of cancer for examination.
Claim 17 depends from claim 13 and requires the method to be an in vitro or ex vivo method.
Claims 21 and 22 depend directly or indirectly from claim 13 and further define the HDAC6 inhibitor. As noted above, Applicant has elected the last option in claim 21 (i.e., ITF3756) as the species of HDAC6 inhibitor for examination.
Claims 23-25 depend directly or indirectly from claim 13 and requires the expression level to be/to have been measured in a particular type of biological sample.
Claims 14, 17, 21-25, 27, and 28 each recite a plurality of judicial exceptions for the same reason as claim 13. More specifically, the correlation between the RNA biomarker expression level and the efficacious dose and/or biological activity of the HDAC6 inhibitor is a natural law, and the “determining” and “comparing” steps in claim 13 encompass at least one abstract idea (mental step and/or mathematical calculation).
Claims 14, 17, 21-25, 27, and 28 are not integrated into a practical application for the same reasons set forth above with respect to claim 13. That is, the claims do not use the judicial exceptions to perform any useful application (e.g., altering the treatment of a patient). As well, claims 14, 17, 21-25, 27, and 28 do not contain any elements that would cause them to amount to significantly more than the judicial exception since they only further define the judicial exception in various ways. More specifically, claims 14 and 17 only further define the judicial exception by limiting the type of data that is analyzed (i.e., by requiring analysis at a particular time point) or the environment for the analysis (i.e., in vitro or ex vivo), respectively. Claims 21, 22, 27, and 28 only further define the judicial exception by reciting the elected species of HDAC6 inhibitor (claims 21 and 22) or the elected species of cancer (claims 27 and 28). Claims 23-25 only further define the judicial exception by limiting the sample type.
Claims 15 and 16
Claim 15 depends from claim 13 and require an additional step of “classifying the patient as responsive or non-responsive to a therapeutic treatment.” Claim 16 depends from claim 15 and requires the classification to be “based on whether the expression value of the at least one RNA biomarker is above or below a threshold expression value.”
These claims each recite a plurality of judicial exceptions for the same reason as claim 13. As well, the additional classifying step recited in claims 15 and 16 is an abstract idea because it encompasses a mental step and/or a mathematical calculation.
Claims 15 and 16 are not integrated into a practical application for the same reasons set forth above with respect to claim 13. That is, the claims do not use the judicial exceptions to perform any useful application (e.g., altering the treatment of a patient). As well, claims 15 and 16 do not contain any elements that would cause them to amount to significantly more than the judicial exception since they only recite an additional judicial exception.
Claim 26
Claim 26 depends from claim 23, which depends from claim 13, and requires the expression level of the at least one RNA biomarker to be detected by RNA sequencing, quantitative RT-PCR, digital PCR, use of an Affymetrix microarray or a custom microarray, or via nanostring technology.
Claim 26 recites a plurality of judicial exceptions (abstract ideas) that are not integrated into a practical application for the reasons set forth above with respect to claim 13. It is noted that, unlike claim 13, claim 26 does require a step of measuring the expression level of the elected RNA biomarker.
The detection methods recited in claim 26 are additional elements that must be considered as part of the analysis in Eligibility Step 2B (see MPEP 2106.05), but each of the methods recited in claim 26 is a routine and conventional method for measuring RNA expression levels as evidenced by the following references: (i) Eastel et al. (Expert Review of Molecular Diagnostics 2019; 19: 591-598) (see, e.g., abstract and sections 2-3 and 7-8 and Table 5); (ii) Angerer et al. (Current Opinion in Systems Biology 2017; 4: 85-91) (see, e.g., the “The growth of single-cell transcriptomics” section on pages 85-87); (iii) Wang et al. (Frontiers in Oncology 2020; 10: Article 447) (see, e.g., the abstract); and (iv) Narrandes and Xu (Journal of Cancer 2018; 9: 2249-2265) (see, e.g., the abstract, pages 2250-2255, and Table 1 on page 2258). Accordingly, claim 26 does not amount to significantly more than the judicial exceptions.
Thus, claims 13-17 and 21-28 are rejected under 35 U.S.C. 101 as being directed to ineligible subject matter.
Claim Rejections - 35 USC § 112
10. 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 13-17 and 21-28 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.
Claim 13 is indefinite because it is unclear as to how the recited method steps achieve the objective stated in the preamble of “evaluating the efficacious dose and/or the biological activity of an HDAC6 inhibitor.” Claim 13 only requires determining the expression level of one or more RNA biomarkers in a patient sample and comparing said expression level with that of a reference sample. There is no requirement for the patient to be treated (currently or previously) with the HDAC6 inhibitor. As a result, it is not clear as to how steps (a) and (b) in claim 13 allow one to assess the dose and/or biological activity of an HDAC6 inhibitor as stated in the preamble. Applicant could address the issue by amending claim 13 to clearly require the patient to have been treated or to be currently undergoing treatment with an HDAC6 inhibitor.
Claims 14-17 and 21-28 are also indefinite because they depend from claim 13 and do not correct its indefiniteness issues. And more specifically as to claims 14-16, it is noted that these claims also do not clearly require administration of an HDAC6 inhibitor to the patient. Therefore, although they require evaluation during or after a therapeutic treatment (claim 14) or classifying the patient as responsive or non-responsive to treatment (claims 15 and 16), they do not remedy the indefiniteness issue in claim 13 discussed above.
Claim 26 is also indefinite for an additional reason. In particular, this claim contains the following trademarks/trade names AFFYMETRIX and NANOSTRING. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a particular brand of microarray or a particular type of nucleic acid detection, respectively, and, accordingly, the identification/description is indefinite.
Conclusion
11. No claims are currently allowable. The elected species is free of the prior art, but the claims are rejected for other reasons.
Karikoski et al. (Clinical Cancer Research 2014; 20: 6452-6464) and Kzhyshkowska (The Scientific World Journal 2010; 10: 2039-2053) are cited as prior art references of interest for their teachings regarding the biological role of the elected STAB1 gene.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Angela Bertagna whose telephone number is (571)272-8291. The examiner can normally be reached 8-5, M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANGELA M. BERTAGNA/Primary Examiner, Art Unit 1681
1 It is noted that claims 18-20 require analysis of the elected RNA biomarker (STAB1). These claims are nevertheless withdrawn from consideration because they require analysis of non-elected RNA biomarkers in addition to the elected RNA biomarker.
