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 .
Priority
The instant application, filed April 23rd, 2024, is a 371 filing of PCT/JP2022/039851, filed October 26th, 2022, and claims domestic benefit to US provisional application 63/272,499, filed on October 27th ,2021.
Status of Claims/Application
Applicant filed an amendment to the claims on April 23rd, 2024. Claims 9-11 are cancelled. Claims 1-8 are original. Claims 1-8 are pending and examined under the merits herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on October 9th, 2025 and April 23rd, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
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.
Claim 4 and 5 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception(s) (i.e., a law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. Abstract ideas include mathematical concepts (including mathematical relationships, formulas, equations, and calculations), mental processes (including concepts performed in the human mind), and certain methods of organizing human activity (including managing personal behavior, relationships, or interactions between people).
The claim 4 recites a method for determining a renal prognosis by calculating a ratio between an expression amount of MGAM and an expression amount of MUC1 in urinary extracellular vesicles derived from a subject, and determining a poor prognosis when the ratio is equal to or greater than a threshold. Claim 5 which depends on claim 4 recites the urinary extracellular vesicles are phosphatidylserine-positive.
Claim 4 is directed to a judicial exceptions as the method steps refer to a natural phenomenon (“determining the expression amount of MGAM and MUC1 in urinary extracellular vesicles” and “determining poor prognosis based on the level of MGAM and MUC1 ratio” is a correlation between a trend and a disease), and an abstract idea (“calculating a ratio between an expression amount of MGAM and MUC1”, “determining a poor prognosis” which is a mental step) (STEP 2A prong 1: Yes).
Claim 4 does not recite additional elements that integrate the judicial exception into practical application and there are no additional elements recited that is sufficient to amount to significantly more than the judicial exception (Step 2A prong 2: No and Step 2B: No). Claim 5 recites an additional element (“the urinary extracellular vesicles are phosphatidylserine-positive”) but is still directed to the judicial exception(s) (i.e., a law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. Claim 5 recites the property of the extracellular vesicle as phosphatidylserine positive and in the instant specification does not further disclose any additional elements that integrate the judicial exception into a practical application (page 13, paragraph 0021).
Therefore, the judicial exceptions recited in Claim 4 and 5 are not integrated into practical application (STEP 2A prong 2: no) because the additional elements (when considered individually and in combination) is not sufficient to amount to significantly more than the judicial exception because the limitations merely recite the words "apply it" (or an equivalent) with the judicial exception, or merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f).
The recited steps in claim 4 and 5 impose no meaningful limit on the scope of the claims and are recognized at a high level of generality such that substantially all methods of measuring MUC1 and MGAM expression on urinary extracellular vesicles of a subject would conventionally and routinely perform such steps. Further, the instant specification discloses the MUC1 and MGAM expression on urinary extracellular vesicles can be measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) (page 15, line 10-11) and immunoassays like ELISA using an anti-MUC1 antibody (page 19, line 15). These techniques are well-known, routine, and conventional means of measuring MUC1 and MGAM in samples as evidenced by Raby (Raby, Katie Louise. “Urinary Exosomes Protein Cargo as Biomarkers of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Doctoral Thesis (Ph.D.).” UCL (University College London)., 2019. See page 101, 4.1.2 Proteomic analysis of urinary exosomes) and Budiu (Budiu RA, Mantia-Smaldone G, Elishaev E, Chu T, Thaller J, McCabe K, Lenzner D, Edwards RP, Vlad AM. Soluble MUC1 and serum MUC1-specific antibodies are potential prognostic biomarkers for platinum-resistant ovarian cancer. Cancer Immunol Immunother. 2011 Jul;60(7):975-84. doi: 10.1007/s00262-011-1010-x. Epub 2011 Apr 2. PMID: 21461842; PMCID: PMC11029120. See page 1, abstract “we measured antigenic levels […] by ELISA”). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (common methods of detecting expression) are routinely performed in the art to obtain data regarding expression and treat subjects (STEP 2B: No). In regards to “diagnosing", it is further noted that merely presenting results of a process otherwise unpatentable under 35 U.S.C. 101 is insufficient to establish eligibility under the statute. See FairWarning IP, LLC v. Iatric Sys., Inc., No. 2015-1985, 2016 WL 5899185, at *3 (Fed. Cir. Oct. 11, 2016) (claim unpatentable under 35 U.S.C. 101 despite recitation of the step: “providing notification if [an] event has occurred”). Moreover, “[w]hile preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility…." Ariosa Diagnostics, Inc., v. Sequenom, Inc., 788 F.3d 1371, 1379 (Fed. Cir. 2015), cert. denied, No. 15-1182, 2016 WL 1117246 (U.S. June 27, 2016). Further, “Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the § 101 inquiry.” Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2117 (2013).
The claims 4 and 5 do not recite something “significantly more” than the judicial exception(s); rather, the claims “simply inform” the natural phenomenon to one performing routine active method steps and do not amount to significantly more than the judicial exception(s).
Claim Rejections - 35 USC § 103
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.
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.
Claims 1, 2, 3, 6, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Maney (WO 2014/193999 A2, published in December 4th, 2014) and further in view of Tomiyama (Tomiyama, E., Fujita, K., Nonomura, N. (2021). Urinary Extracellular Vesicles: Ultracentrifugation Method. In: Salvi, S., Casadio, V. (eds) Urinary Biomarkers. Methods in Molecular Biology, vol 2292. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1354-2_15).
Regarding claims 1, 2, and 3, Maney recites a method for detecting kidney disease/injury by analyzing circulating biomarkers such as a vesicle in a biological sample (page 2, paragraph 0010, “Disclosed herein are methods and compositions for characterizing a phenotype by analyzing circulating biomarkers, such as a vesicle, microRNA or protein present in a biological sample” and page 23, Table 1: Examples of Biological Samples for Vesicle Analysis for Various Diseases, Conditions, or Biological States, “Kidney disease/injury: …” and “urine”, see figure 1 of this office action).
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Figure 1. Maney, page 23 Table 1
Further, Maney discloses the method of detecting a mucin protein MUC1 in the biological sample (page 2, paragraph 0011, “the invention provides a method for detecting a biomarker in a biological sample, comprising: contacting the biological sample with at least one binding agent specific to the biomarker, wherein the biomarker is selected from the group consisting of a mucin protein”) and page 2, paragraph 0013, “The mucin protein may comprise MUC1”). It is noted that Maney also teaches the MGAM marker (page 93, Table 5: Illustrative Biomarkers, under prostate cancer vesicle markers).
Further, Maney teaches biological sample are the urinary extracellular vesicles (page 31, paragraph 00129, “In addition, vesicles from a biological sample such as urine may be isolated by differential centrifugation followed by contact with antibodies directed to cytoplasmic or anti-cytoplasmic epitopes as described in Pisitkun et al, Proc Natl Acad Sci USA, 2004;101:13368-13373”).
Maney teaches that the urinary vesicles are phosphatidylserine-positive as well as that the marker protein is CD9 (page 25, Table 2: Vesicle Properties, “PPS -phophatidylserine”, “major protein markers: CD9 under exosomes” see figure 2 of this office action, and paragraph 0020, “The methods of the invention may further comprise contacting the biological sample with at least one additional binding agent specific to an additional biomarker. In some embodiments, the additional biomarker comprises a microvesicle antigen. The additional biomarker can be a biomarker selected from Table 3, Table 4, and/or Table 5 herein. The additional biomarker can be a protein selected from the group consisting of a tetraspanin, CD9,”).
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Figure 2. Maney page 25, Table 2: Vesicle Properties
Regarding claims 6, 7, and 8, Maney teaches a detection kit for kidney dysfunction diagnostic marker, the kit comprising an anti-MUC1 antibody and/or an anti-MGAM antibody (page, paragraph 00774, “The kits provided by the invention can comprise a device, wherein the device comprises a substrate disposed with a biomarker or to a ligand that is configured to bind a biomarker. The kits can be used in methods of isolating one or more selected subpopulation of vesicles from a biological source, such as a cell culture, tissue sample, or bodily fluid”). Maney teaches the anti-MUC1 antibody (page 306-310, Table 43, See Figure 3 of this office action).
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Figure 3. Table 43 of Maney (page 306-310) listing anti-MUC1 antibodies used to detect MUC1
However, Maney does not teach the substance having affinity for urinary extracellular vesicles is Tim4. Tomiyama teaches Tim4 to purify urinary extracellular vesicles without ultracentrifugation (page 173, title and page 174, paragraph 1, “we adopted a non- ultracentrifugation approach, called phosphatidylserine (PS) affinity method, which is performed the EV purification based on magnetic beads coated with a phosphatidylserine (PS)-binding receptor protein. In particular, the protein Tim4 specifically binds the PS displayed on the surface of EVs” ). Further, Tomiyama discloses that the PS-Tim4 affinity method yielded more EVs and does not require ultracentrifugation machine (page 175, paragraph 1, “Western blot analysis revealed that the yield of EVs (particularly exosomes) isolated by the PS affinity method was higher than that by ultracentrifugation. Another advantage of the PS affinity method is that EVs can be isolated without an ultracentrifuge machine”). Therefore, it would have been obvious to the person of ordinary skill in the art to combine the method of isolating EVs using Tim4 taught by Tomiyama in the kit with the anti-MUC1 and/or anti-MGAM antibody to measure a kidney dysfunction diagnostic marker as taught by Maney.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lam Thuy Vi Tran Ho whose telephone number is (571)272-9135. The examiner can normally be reached Monday-Friday 7:30-3.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAM THUY VI TRAN HO/Examiner, Art Unit 1647 /L.T./Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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