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, species hsa-miR-18b-3p in the reply filed on 1/9/2026 is acknowledged.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 is missing a preposition between “obtaining a measurement” and “the expression of”. The claim currently directs “obtaining a measurement…the expression of” and would be more grammatically correct if it read “obtaining a measurement, in a biological sample…, of the expression,” for example. Claim 21 is objected to for the same issue in both obtaining steps.
Appropriate correction is required.
Improper Markush Grouping Rejection
Claims 1-11 and 21-23 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of different miRNA listed in the alternative is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The miRNAs do not all share the same structure, namely each has a unique nucleotide sequence. The mere fact that they are all miRNA does not explain their common utility because not all miRNA would be expected to function in the claimed methods. There is no expectation from the prior art that they would all function in the same way.
Furthermore, with regard to common function, the specification does not provide data to support that all of these miRNA would function predictively in the claimed method in the same way, that is with similar or the same predictive relationship.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
With regard to claim 5, it is noted that all combinations which include elected 18b-3p are considered a proper grouping since they all include on common structural element. Within this claim the combinations that include the elected combination have been considered.
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 1-11 and 21-23 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 1 recites administering a treatment indicated in guidelines provided by “Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO).” However, this is indefinite because it is not clear which guidelines are being referred to, the MASCC/ISOO has many working groups and presumably guidelines for each. Therefore, it is unclear what treatment is intended or required when applicant refers to “a treatment indicated” by in guidelines provided by MASCC/ISOO.
Claim 1 requires obtaining expression “of an miRNA,” but then refers to “of said miRNAs” in the “identifying” step. The phrase “said miRNAs” lacks proper antecedent basis because the claim does not previously recite or require measuring the expression of more than one miRNA.
In claim 3 it is unclear what it means for “one, more than one of the miRNAs or all of the miRNAs” to “comprise of hsa-miR-18b-3p.” The language of the claim is unclear because it is not clear what it means to “comprise of” a miRNA. It is especially no clear how “more than one” or “all said” miRNA can “comprise of” a single miRNA. Furthermore, it is noted that “the miRNAs” is confusing because the claim previously only requires measuring the expression of “an miRNA.”
Claim 4 is confusing because it depends from claim 1 but recites that the step of measuring the expression is carried out “only in at least one biological sample taken after the antitumor therapy” but claim 1 clearly requires measuring expression in samples before and after antitumor therapy, so it is not clear what is meant by “only in at least one.” Furthermore, it is not clear how “more than one” or “all of the miRNAs” can consist of the single listed miRNA. If there is more than on miRNA being measured, how can it consist of only one miRNA?
Regarding claims 6, 8, 10, and 11, the phrases "preferably" and “such as” and “for example” render the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
In claim 9, it is unclear what is required for a method to be carried out by “Microarray” since microarray is not a method but a product.
Claim 21 requires obtaining expression “of an miRNA,” but then refers to “of said miRNAs” in the “determining” step. The phrase “said miRNAs” lacks proper antecedent basis because the claim does not previously recite or require measuring the expression of more than one miRNA.
Any claim not specifically addressed is rejected because it depends from a rejected claim.
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 1-11 and 21-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to law of nature and an abstract idea without significantly more. The claim(s) recite(s) identifying a change in the expression of miRNA in a before and after sample, which is an abstract idea that is a mathematical process. Claims 1-11 further set forth that the change indicates mucositis which is a naturally occurring correlation. This judicial exception is not integrated into a practical application because although claim 1 recites three options for treatment, the first option is not specific to mucositis, as the guidelines are not recited to be guidelines for treatment of mucositis, and furthermore, the treatments in the guidelines lack adequate definiteness and written description. The treatment step in claim 21 does not integrate the judicial exception because it occurs during a data gathering step and does not apply or use the judicial exception in any way. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps in addition to the judicial exception are routine data gathering steps recited at an extremely high level of generality with regard to technique and sample used. For example, Kahraman et al. (cited herein) teaches detecting microRNA expression in liquid biopsies using commercially available microarrays.
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 1-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The contents of the guidelines provided “Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO)” is considered essential material in accordance with 37 CFR 1.57(d) since knowledge of the particular treatments is necessary to describe the claimed invention in terms that particularly point out and distinctly claim the invention as required by 35 USC 112(b) and to provide a written description of the claimed invention. See MPEP 608.01(p)(I)(A).
The originally filed specification (6/15/2023 in the electronic file; which is a copy of the specification filed in the PCT) teaches administering a specific treatment for the prevention and treatment of mucositis, and gives as an example “the ones indicated in the guidelines provided by” MASCC/ISOO, but it fails to incorporate this information by reference, and further it fails to specifically identify the document, such as by date and publication information, and there were multiple guidelines present in the prior art. It is not permissible to incorporate essential subject matter from a non-patent reference, and additionally, there is a lack of clarity in the disclosure as to which guidelines were being referred to as “the guidelines.” There is no indication in the original disclosure of an intention to incorporate this subject matter by reference, and “[m]ere reference to another application, patent, or publication is not an incorporation of anything therein into the application containing such reference for the purpose of the disclosure required by 35 U.S.C. 112.” See MPEP 608.01(p)(I)(A). Therefore, these claims are rejected as lacking written description because the disclosure does not provide adequate support for the essential subject matter.
Claims 1-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims recite a method for diagnosis and treatment of mucositis in a cancer patient undergoing cancer treatment and include identifying a change in the expression of has-miR-18b-3p (consonant with the election) as an indicator of mucositis, and then treating the patient.
However, the specification does not provide any data to support that a change, either upregulation or downregulation, in the expression of the miR is indicative of mucositis.
The specification shows in the examples that the miR differentially expressed in response to neoplastic agents, specifically the miR was upregulated relative to control, irrespective of the type of treatment (p. 24, line 6). However, the disclosure does not provide any data to demonstrate that this upregulation is related to the development of mucositis or if it occurs in all patients regardless of whether or not mucositis develops.
The specification additionally shows that in three out of only four patients tested, an increase in the levels of circulating hsa-miR-18b-3p was detected (p. 25, line 5). The specification hypothesizes that "the interpatient differences in expression levels might in some way be linked to the patient's susceptibility to developing oral mucositis and/or the degree or severity thereof." The disclosure does not provide any technical support and/or evidence of an association between the levels of the specific miRNA has-miR-18b-3p and the presence or diagnosis of mucositis of a cancer patient. Not all cancer patients undergoing antitumor therapy develop mucositis. Whether the disreguation of the elected miRNA inevitably results in oral or intestinal mucositis, or predicts which treated patients will develop one of these, is unpredictable based on the evidence of record.
Gutierrez-Camino (2018; IDS 6/15/23) teaches that 206 miRNA were screened to determine a predictive marker of mucositis in pediatric acute lymphoblastic leukemia (ALL) patients. Of the 206 potential markers tested, only three were potential hits as being predictive of mucositis. Gutierrez-Camino (2017; IDS 6/15/23) demonstrates unpredictability of identifying diagnostic biomarkers. The reference attempted to validate the results of a prior study connecting polymorphisms in miRNA to the development of mucositis in pediatric acute lymphoblastic leukemia (ALL) patients. Of five previously identified markers, only one was able to be confirmed as a potential diagnostic marker. These references together demonstrate that it is highly unpredictable whether any putative marker will itself be a diagnostic marker for mucositis, and that such a predictive relationship must be determined empirically using appropriate case-controlled studies.
Given the level of unpredictability in the art, and the lack of evidence to support the assertion that the expression of the miR is associated with mucositis, the practice of the claimed invention would require carrying out appropriate case-controlled studies covering a variety of types of cancer, treatments and types of mucositis (oral versus GI). It is unpredictable which of these studies would result in finding a predictive relationship between expression levels of the miR before and after treatment. This experimentation, considering the number of variables concerned would require an enormous amount of work, where it is highly unpredictable if the outcome will be successful.
Thus, having carefully considered the data provided in the disclosure, the high level unpredictability in the art, and the amoung of experimentation required to practice the invention, it is concluded that it would require undue experimentation to practice the claimed invention.
Claim Rejections - 35 USC § 102
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) 21, 22, and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kahraman et al. (Scientific Reports | (2018) 8:11584 | DOI:10.1038/s41598-018-29917-2; 11 pages, and supplemental table 1).
The reference teaches measuring in a blood sample (a liquid biopsy) the expression of miR-18b-3p, subjecting the subject to treatment with paclitaxel (an antimitotic chemotherapy), obtaining a second measurement in blood of the expression of the miRNA, and determining whether a change has occurred. See p.2, study set up, patient characteristics and p. 3, miRNA measurement on microarrays. Evidence that miR-18b-3p expression was measured is in the supplemental table attached to the paper, which reports data for this miR on the 16th page of the table.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682