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 .
Duplicate Claim Warning
Applicant is advised that should claims 1, 33, and 34 be found allowable, claims 11, 31, and 32 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Specifically, claim 1 recites in step (i) the level of the lysosomal system marker being determined following treatment of the sample of whole blood with an inhibitor. Dependent claim 11 recites the method according to claim 1, wherein the method comprises, prior to step (i) treating the sample of whole blood with the inhibitor of lysosomal system function. As such, claim 11 recites twice the step of treating the sample of whole blood with the inhibitor. Claims 33-34 are dependent from claim 1 and claims 31-32 are dependent from claim 11.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 8, 2026 has been entered.
Status of the Claims
Claims 1-11 were pending. Claims 1, 2, and 11 are amended. Claims 3-7 are cancelled. Claims 22-34 are added.
Claims 1, 2, 8-11, and 22-34 are examined herein.
Withdrawn Rejections
The objection to claims 1 and 11 is withdrawn in view of claims amendments.
The rejections of claims 1, 2, 8-11 under 35 U.S.C. §103 are withdrawn in view of claims 1 and 11 amendments.
The objections and rejections of claims 3-7 are withdrawn in view of claims cancellation.
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, 2, 8-11, and 22-34 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.
Claim 1 recites a method of assessing lysosomal system flux in a subject comprising treatment of the sample of whole blood with an inhibitor of lysosomal system function.
The specification only discloses evidence obtained from human subjects. The art of cellular regulation and metabolism as evidenced by the existence of different animal models to study different human diseases is unpredictable and one of ordinary skill in the art cannot reasonably expect this method applicable to subjects other than human.
Additionally, the recited method of assessing lysosomal system flux in a subject implies that this method assesses lysosomal system flux of the subject. The specification discloses only evidence obtained from experiments with peripheral blood mononuclear cells. No other cell types or tissues have been tested. Cellular metabolism in peripheral blood mononuclear cells cannot be extrapolated to the entire human subject where different kinds of cells and tissues can have their own lysosomal system fluxes and there is no lysosomal system flux that characterizes the entire human subject. Therefore, the flux measured in peripheral blood mononuclear cells cannot be the flux of a human subject.
Additionally, Klionsky et al. (IDS; Autophagy. 2012 Apr;8(4):445-544.) teach that in some cell types a subpopulation of LC3-II exists in a cytosolic form (pg. 47, col. 1, par. 2). Therefore, a direct measurement of LC3-II biomarker may lead to overestimation of the autophagic flux in these cell type subpopulations.
Claim 2 recites the inhibitor of lysosomal system function comprises one or more of chloroquine, bafilomycin A1, E-64d, and pepstatin A.
The specification discloses evidence for chloroquine (Examples 1-3) and bafilomycin (Example 3). No other inhibitors have been tested by Applicant. The problem with instant disclosure is in the limitation of treating the whole blood with the recited inhibitors. While chloroquine and bafilomycin can readily penetrate the cell membrane, E-64d and pepstatin A are not known for such properties. In fact, pepstatin A is known for its “low permeability across the cell membrane” (BenchChem Technical Support Team; pg. 1, last par.). The art is unpredictable as inhibitor molecules with different structures do not necessarily have similar membrane-penetrating properties and one of ordinary skill in the art cannot reasonably expect E-64d and pepstatin A inhibitors readily penetrating the cell membrane and inhibiting lysosomal system function.
Claims 2, 8-11, and 22-34 are rejected because they depend from rejected claim 1.
Based on the above findings, one of ordinary skill in the art would conclude that Applicant did not have possession of the claimed invention at the time the application was originally filed.
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, 2, 8-11, and 22-34 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring correlation, without significantly more.
Claim 1 is directed to a process, which belongs to the four statutory categories.
The claim is related to a method of establishing relationship between the level of the lysosomal system marker LC3B-II and the lysosomal system flux in peripheral blood mononuclear cells.
This relationship is categorized as a naturally occurring correlation, and therefore it is a judicial exception.
The claim also recites additional steps of determining, comparing, and assessing.
The additional step of “determining” comprising a treatment step with an inhibitor is an insignificant extra-solution activity that amounts to mere data gathering necessary to apply the judicial exception.
The additional steps of “comparing” and “assessing” amount to making a conclusion based on the results of the biomarker level measurements. These steps are performed in the human mind and considered an observation, evaluation, and/or a judgement. They fall into the mental process groupings of abstract ideas and therefore are judicial exceptions.
The claim fails to recite a step of using the assessed flux values for a practical application, such as treating the subject. Therefore, the claim does not integrate the recited judicial exceptions into a practical application and the claim is directed to the judicial exceptions.
Additional elements of measuring the biomarker levels are recited at a high level of generality. Claim 1 does not recite any specific measurement methods and dependent claims 8-10 recite well-known immunological methods for measuring biomarker levels: ELISA, immunocytochemical staining, and Western blotting. Such measurements have been recognized as routine laboratory techniques.
The techniques for measuring a level of LC3B-II are known in the art. It was routine and conventional to measure LC3B-II levels in biological samples using western blotting (Chittaranjan et al. Cold Spring Harb Protoc. 2015 Aug 3;2015(8):743-50). Chittaranjan teaches a method for “Monitoring Autophagic Flux by Using Lysosomal Inhibitors and Western Blotting of Endogenous MAP1LC3B” (Title). The reference teaches monitoring of autophagic flux using LC3B-II as a lysosomal system marker, and LC3B-II levels were determined by western blotting (Abstract).
Therefore, the claims as a whole do not amount to significantly more than the recited exceptions, because there are no additional elements, or combination of additional elements, that add an inventive concept to the claims and are not routine and conventional.
The dependent claims 2, 8-11, and 22-34 fail to add additional elements, or combination of additional elements, that contribute to an inventive concept to the claim.
For these reasons, claims 1, 2, 8-11, and 22-34 are ineligible under 35 U.S.C. 101.
Response to Arguments
Applicant’s arguments and the Affidavit filed on September 8, 2026 have been fully considered.
Applicant’s amendments to claim 1 overcome the rejections of claims 1, 2, 8-11 under 35 U.S.C. §103; therefore, the rejections are withdrawn. The prior art does not teach or suggest a method of assessing lysosomal system flux in a subject comprising determining the level of a lysosomal system marker LC3B-II in peripheral blood mononuclear cells following treatment of the sample of whole blood with an inhibitor of lysosomal system function.
All other arguments are moot because the rejections have been withdrawn.
Subject Matter Free of the Prior Art
Claims 1, 2, 8-11, and 22-34 are free of the prior art.
Prior art is silent on a method of assessing lysosomal system flux in a subject comprising determining the level of a lysosomal system marker LC3B-II in peripheral blood mononuclear cells following treatment of the sample of whole blood with an inhibitor of lysosomal system function.
The closest prior art:
Chittaranjan et al. (Cold Spring Harb Protoc. 2015 Aug 3;2015(8):743-50) teach monitoring autophagic flux by using lysosomal inhibitors and Western blotting (Title) in primary or cultivated cells but fail to teach measuring LC3B-II levels in peripheral blood mononuclear cells following treatment of the sample of whole blood with an inhibitor of lysosomal system function;
Gaber et al. (PGPub 20190072567) teach detecting LC3B expression in isolated exosomes but fail to teach measuring LC3B-II levels in peripheral blood mononuclear cells following treatment of the sample of whole blood with an inhibitor of lysosomal system function;
Yoshii et al. (IDS; Int J Mol Sci. 2017 Aug 28;18(9):1865) teach monitoring and measuring autophagy using LC3 biomarker in cultured cells (pg. 4, par. 2) but fail to teach measuring LC3B-II levels in peripheral blood mononuclear cells following treatment of the sample of whole blood with an inhibitor of lysosomal system function;
Groeneveld et al. (IDS; Research and Practice in Thrombosis and Haemostasis, Vol. 1, Supp. 1, pp. 1238-9) teach disruption of the autophagy machinery by treating plasma or whole blood from healthy volunteers with different concentrations of chloroquine or bafilomycin A1 (pg. 1239, col. 1, par. 3) but fail to teach measuring LC3B-II levels in peripheral blood mononuclear cells.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/
Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677
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