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 .
Detailed Action
The Amendments and Remarks filed 11/19/25 in response to the Office Action of 5/19/25 are acknowledged and have been entered.
Claims 1-3 and 5-18 are pending.
Claims 1, 2, and 9-12 have been amended by Applicant.
Claims 1-3 and 5-18 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Rejections Withdrawn
The rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn.
The rejections under 35 U.S.C. 103(a) are withdrawn.
The rejection of claim 8 under 35 U.S.C. 101 is withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 101
Claims 1-3, 5, 7, and 9-16 remain rejected and claim 6 is 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 rationale for this determination is explained below:
Claims 1-3, 5-7, and 9-16 are directed to abstract idea and natural phenomenon because the claims recite natural phenomenon and an abstract idea (“Step 2A prong one”) and the judicial exception(s) is/are not integrated into a practical application (“Step 2A prong two”). The “natural phenomenon” includes: PolySialic Acid is present in biological samples; levels of extracellular vesicles triple-positive for polySia, STEAP1, and PSMA are indicative of prostate cancer; levels of extracellular vesicles triple-positive for polySia and mammaglobin A are indicative of breast cancer; and cancer extracellular vesicles are positive for polySia and tissue-specific biomarkers. The “abstract ideas”, all mental processes, include the “comparing” and “selecting” steps of claim 1 and the “quantifying” step of claim 12. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception(s). A claim that focuses on judicial exception(s) can be shown to recite something “significantly more” than the judicial exception(s) by reciting a meaningful limitation beyond the judicial exceptions. However, in the instant case, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (when considered both individually and as an ordered combination) are limited to well-understood, routine and conventional limitations of detecting biomarkers, such as STEAP1, PSMA, mammaglobin A, and/or polySia in biological samples (“Step 2B”). Such detection of biomarkers in biological samples is well-understood, routine, and conventional in the art. Well-understood, routine and conventional limitations are not meaningful limitations and are not enough to qualify the claimed method as reciting something “significantly more” than the judicial exception(s) (see Part I.B.1 of the interim Guidance).
MPEP 2106.05(d)(II) provides a non-limiting list of laboratory techniques recognized by courts as well-understood, routine, conventional activity. These techniques include:
i. Determining the level of a biomarker in blood by any means, 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);
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Here, the claims do not contain any significant additional elements or steps beyond the observation of judicial exception(s) present when performing routine and conventional methods. Further, the active method steps are conventional and routine in the art for the reasons stated above and the claims do not amount to significantly more than the judicial exception(s). Further, just as methods comprising detecting paternal DNA sequences in particular samples by PCR was identified in Ariosa v. Sequenom as "well-known, routine, and conventional" (see first paragraph on page 13 of Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015)) even though the prior art did not demonstrate detecting said paternal DNA sequences in said particular samples by PCR, the methods encompassed by the instant claims are well-known, routine, and conventional. 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 known biomarkers and/or extracellular vesicles that express such biomarkers) are routinely performed in the art to obtain data regarding expression. 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 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).
Response to Arguments
In the Reply of 11/19/25, Applicant indicates the rejection should be withdrawn because the claims constitute patentable subject matter and are not directed to natural phenomenon and an abstract idea.
The amendments to the claims and the arguments found in the Reply of 11/19/25 have been carefully considered, but are not deemed persuasive. In regards to the indication the rejection should be withdrawn because the claims constitute patentable subject matter and are not directed to natural phenomenon and an abstract idea, claims 1-3 and 5-16 are directed to abstract idea and natural phenomenon because the claims recite natural phenomenon and an abstract idea (“Step 2A prong one”) and the judicial exception(s) is/are not integrated into a practical application (“Step 2A prong two”). The “natural phenomenon” includes: PolySialic Acid is present in biological samples; levels of extracellular vesicles triple-positive for polySia, STEAP1, and PSMA are indicative of prostate cancer; levels of extracellular vesicles triple-positive for polySia and mammaglobin A are indicative of breast cancer; and cancer extracellular vesicles are positive for polySia and tissue-specific biomarkers. The “abstract ideas”, all mental processes, include the “comparing” and “selecting” steps of claim 1 and the “quantifying” step of claim 12. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception(s). A claim that focuses on judicial exception(s) can be shown to recite something “significantly more” than the judicial exception(s) by reciting a meaningful limitation beyond the judicial exceptions. However, in the instant case, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (when considered both individually and as an ordered combination) are limited to well-understood, routine and conventional limitations of detecting biomarkers, such as STEAP1, PSMA, mammaglobin A, and/or polySia in biological samples (“Step 2B”). Such detection of biomarkers in biological samples is well-understood, routine, and conventional in the art. Well-understood, routine and conventional limitations are not meaningful limitations and are not enough to qualify the claimed method as reciting something “significantly more” than the judicial exception(s) (see Part I.B.1 of the interim Guidance).
It is noted amended claims specify detection methods use “antibodies specific for polySia” to detect PolySialic Acid (polySia); however, using antibodies specific for polySia to detect polySia is certainly conventional and routine (see Figure 3 of Glaser et al (Stem Cells, 2007, 25: 3016-3025) and Figure 1 of Kojima et al (J Biochem, 1998, 124: 726-737), for example).
Double Patenting
Claims 12-14 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11448650 B2. The patent claims and the instant claims are related in that (i) the patent discloses extracellular vesicles are about 50 nm to about 1400 nm in size (lines 57-61 of column 7, for example) and the patent claims require a step of “providing a subject identified as having at least 2,000 prostate cancer extracellular vesicles that are triple-positive for polySia, STEAP1, and PSMA per microliter of biological sample” and (ii) the instant claims are drawn to a method of detecting cancer, including prostate cancer, extracellular vesicles that are positive for polySia (and/or triple-positive for polySia, STEAP1, and PSMA) by obtaining a biological sample from a subject, detecting extracellular vesicles in the sample, measuring the number of extracellular vesicles per microliter of the biological sample, and quantifying the number of extracellular vesicles per microliter of the biological sample that are about 50 nm to about 1400 nm in size positive for polySia (and/or triple-positive for polySia, STEAP1, and PSMA). One would be motivated by the patent claims (also disclosed by the patent) to perform them methods of the instant claims in order to perform the “providing” step of the patent method.
Response to Arguments
In the Reply of 11/19/25, Applicant requests withdrawal of this rejection in view of a submitted terminal disclaimer.
The amendments to the claims and the submitted terminal disclaimer have been carefully considered, but are not deemed persuasive. The terminal disclaimer filed on 11/19/25 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of the statutory term of patent No. 11448650 has been reviewed and is NOT accepted.
1. The POA submitted on 11/19/25 wasn't accepted by our office. Please reference the letter N572 date 11/21/25 for the reason.
2. The terminal disclaimer identifies a party who is not the applicant (only for applications filed on or after September 16, 2012; See FP 14.26.10): For cases filed on/after 9/16/12, 37 CFR 1.321 specifies that the applicant can disclaim, and the terminal disclaimer must specify the extent of the applicant’s ownership. A request under 37 CFR 1.46(c) to change the applicant needs to be filed, which is (1) a request, signed by a 1.33(b) party, (2) a corrected ADS (37 CFR 1.76(c)) that identifies the “new” applicant in the applicant information, and is underlined since it is new, and (3) a 3.73(c) statement showing chain of title to the new applicant. Along with the § 1.46(c) request we need a POA that gives power to the attorney who is signing the TD, along with another copy of the TD, unless they file a TD that is signed by the applicant.
3. No additional fee is required with the resubmission.
Claims 9, 10, 12-14, 17, and 18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over 1-6 of U.S. Patent No. 11448650 B2, as applied to instant claims 12-14, and in further view of Biggs et al (Oncotarget, 2016, 7(8): 8839-8849). Instant claims 12-14 are discussed above. Instant claims 17-18 are drawn to kits obvious for performing steps for the “providing” step of the patent method. One would have been motivated to perform a method comprising the method of Biggs et al of detecting, characterizing expression of a biomarker on, and quantifying extracellular vesicles in samples by using reagents including fluorophore-labeled antibodies specific for a biomarker of interest on the extracellular vesicles, isotype control antibodies, and calibration beads (pages 8841-8842, in particular) wherein the biomarkers of interest are antibodies specific to each of polySia, STEAP1, and PSMA biomarkers of the patent conjugated to a different fluorophore to permit one to determine whether the extracellular vesicles comprise all three of polySia, STEAP1, and PSMA by detecting three different fluorophores in order to “provide” the subject of the patent. Further one would be motivated to generate a kit with all reagents required for the combined method with written instructions providing the benefit of guidance to perform the combined method.
All reagents of a method are a “kit”. Further, generating a “kit” for a given method provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. Thus, one need not purchase gram quantities of numerous different reagents when each of which may be needed in only microgram amounts, when beginning a series of experiments. When one considers all of the unused chemicals that typically accumulate in weighing rooms, desiccators, and freezers, one quickly realizes that it is actually far more expensive for a small number of users to prepare most buffer solutions from the basic reagents. In actuality, a kit format saves money and resources for everyone by dramatically reducing waste. 2) The other service provided in a kit is quality control. Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to combine the reagents of a method into a kit format since a kit provides a quality control, saves money, and saves resources.
Response to Arguments
In the Reply of 11/19/25, Applicant repeats request addressed above.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112
Claims 1, 2, and 5-8 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.
Claims 1, 2, and 5-7 are rejected because claim 1 recites the limitation “…one or more tissue-specific biomarkers in the biological samples per unit volume in a biological sample obtained from….” There is insufficient antecedent basis for “the biological samples” in the claims.
Claim 8 rejected for reciting “The method of claim 4, wherein….” Claim 4 is cancelled. The metes-and-bounds of claim 8 are unclear because it is unclear which method claim 8 is further limiting.
Conclusion
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.
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/SEAN E AEDER/Primary Examiner, Art Unit 1642