DETAILED ACTION
The amendment filed on 03/02/2026 has been entered. No new matter has been added.
Claims 1-15 and 18-21 are pending.
Applicant’s election without traverse of species (Claim 6), drawn to a method to monitor cancer treatment, in the reply filed on 10/30/2025 is acknowledged.
Claims 1-2, 4-5 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/30/2025.
Claims 6 and 20 are amended in the claim set filed on 03/02/2026.
Claim 21 is canceled in the claim set filed on 03/02/2026.
Claims 3 and 6-15 in the claim set filed on 03/02/2026 are currently under examination.
Response to the Arguments
Objections to the Drawings and Specification in the previously mailed non-final are withdrawn in light of the Drawings and Specification amendments.
Applicant’s arguments regarding previous rejection(s) of claims 3, 6-15 and 21 under 35 U.S.C. 112 (b) have been fully considered but are not fully persuasive. The 35 U.S.C. 112 rejections documented in the previously mailed non-final have been maintained and revised (documented below on Pg. 3-4) in light of applicants claim amendments and arguments on Pg. 9.
Applicant’s arguments regarding previous rejection(s) of claim(s) 3, 6-15 and 21 under 35 U.S.C. 101 have been fully considered and are not persuasive. Applicant’s argument on Pg. 9, states that “Claim 6 has been amended to include the step of treating the subject. It is respectfully submitted that this limitation imposes a meaningful limit on the judicial exception and integrates the recited judicial exception into a practical application”. The 35 U.S.C. 101 rejections documented in the previously mailed non-final have been maintained and revised (documented below on Pg. 5-8) in light of applicants’ amendments and arguments on Pg. 8-9.
Applicant’s arguments regarding previous rejection(s) of claim(s) 3, 6-15 and 21 under 35 U.S.C. 103 have been fully considered and are not persuasive. Applicant’s argument on Pg. 10, states that “Sansone does not teach or suggest claim 6's isolation of "small nucleic acids" from EVs (step (c))”. The 35 U.S.C. 103 rejections documented in the previously mailed non-final have been maintained and revised (documented below on Pg. 9-13) in light of applicants’ amendments and arguments on Pg. 9-10.
The rejections for claims 3 and 6-15 are documented below in this Final Office Action are maintained and revised.
Priority
This application is a U.S. National Stage Filing under 35 U.S.C. 371 from International Application No. PCT/US2021/071910, filed on October 16, 2021, and published as WO 2022/082229 A1 on April 21, 2022, which application claims the benefit of priority of U.S. Provisional Patent Application No. 63/093,004, filed on October 16, 2020. The priority date of claim set filed on March 02, 2026, is determined to be October 16, 2020.
Claim Rejections - 35 USC § 112 (b)
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 3 and 6-15 remain/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 6 is indefinite over the limitation “the subject” (ln 3) because there is no antecedent basis. Furthermore, related to the issue discussed in the preceding paragraph, it is unclear as to whether the subject has cancer, is suspected of having cancer or not suspected of having cancer. Claims 3, 7-15 and 21 depend on claim 6.
Response to Arguments
Applicant' s arguments filed 03/02/2026 (Pg.11-15) with respect to claim 3, 6-15 and 21 have been considered but are not persuasive. To clarify some instances argued in the response filed 03/02/2026 see responses to each argument made by Applicant below:
Applicants’ argument: “The amendment to independent claim 6 (i) provides antecedent basis by reciting "a subject diagnosed with cancer" in the preamble.” (Pg. 9)
Response: Applicant’s arguments rely on language solely recited in preamble recitations in claim(s) as stated in the applicants’ argument above. When reading the preamble in the context of the entire claim, the recitation "a subject diagnosed with cancer” is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02.
Applicants’ argument: “(ii) incorporates the concrete therapeutic modalities previously recited in claim 21, thereby unambiguously defining "treatment" as therapeutic cancer care. Step (f) is revised to "over the course of the cancer treatment or after completion thereof," curing the ambiguity identified by the Examiner.”(Pg. 9)
Response: Applicant’s arguments stated as (ii) and step (f) above has been fully considered and are persuasive, but due to the remaining 35 U.S.C. 112(b) rejection the previous claim rejections are revised and maintained.
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 3 and 6-15 remain/are rejected under 35 U.S.C. 101 because the claimed invention is directed towards abstract ideas of obtaining blood and comparing level of RE DNAs and routine and conventional steps of enriching sample for EVs, isolating small nucleic acids and quantitating RE DNAs, without significantly more. The claim(s) recite(s) abstract ideas and routine and conventional steps. This judicial exception is not integrated into a practical application because no additional elements integrate the judicial exceptions into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional elements are considered significantly more than the judicial exceptions.
Claim analysis
The instant claim 6 is directed towards: A method to monitor cancer treatment in a subject diagnosed with cancer, comprising: a) obtaining a blood or serum sample from the subject; b) enriching the sample for EVs, c) isolating small nucleic acids from b);d) quantitating RE DNAs present in c);e) comparing the level of RE DNAs in said sample to the level of RE DNAs in a control wherein the control does not have cancer, wherein an increase in levels of RE DNAs as compared to the control indicates the subject has cancer; and f) repeating a) to e) at different times over the course of cancer treatment or after completion thereof to determine the effect of the cancer treatment and/or the maintenance of remission in said subject, wherein the cancer treatment is surgery, radiation therapy, bone marrow transplant, immunotherapy, hormone therapy, crvoablation, or chemotherapy.
The a) obtaining a blood or serum sample from the subject and e) comparing the level of RE DNAs in said sample to the level of RE DNAs in a control are abstract ideas.
The b) enriching the sample for EVs, c) isolating small nucleic acids from b); d) quantitating RE DNAs present in c) and f) repeating a) to e) at different times over the course of treatment or after treatment to determine the effect of treatment and/or the maintenance of remission in said subject; “f) repeating a) to e) at different times over the course of cancer treatment or after completion thereof to determine the effect of the cancer treatment and/or the maintenance of remission in said subject, wherein the cancer treatment is surgery, radiation therapy, bone marrow transplant, immunotherapy, hormone therapy, crvoablation, or chemotherapy” are considered to be active steps requiring the analysis of a sample and the types of cancer treatment being monitored in in said subjects. The active steps are routine and conventional as demonstrated by the 35 USC § 103 rejections stated below.
Furthermore, a cancer treatment is not actually claimed as being administered and the types of cancer treatment being monitored in in said subjects are not of a particular treatment.
Dependent claims set forth further limitations about RE DNAs, sample, subject, and cancer.
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case, the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, abstract ideas.
With regard to claim 6, the claim recites “A method to monitor cancer treatment in a subject diagnosed with cancer, comprising: a) obtaining a blood or serum sample from the subject; b) enriching the sample for EVs, c) isolating small nucleic acids from b);d) quantitating RE DNAs present in c);e) comparing the level of RE DNAs in said sample to the level of RE DNAs in a control wherein the control does not have cancer, wherein an increase in levels of RE DNAs as compared to the control indicates the subject has cancer; and f) repeating a) to e) at different times over the course of cancer treatment or after completion thereof to determine the effect of the cancer treatment and/or the maintenance of remission in said subject, wherein the cancer treatment is surgery, radiation therapy, bone marrow transplant, immunotherapy, hormone therapy, crvoablation, or chemotherapy.” The a) obtaining a blood or serum sample from the subject and e) comparing the level of RE DNAs in said sample to the level of RE DNAs in a control are abstract ideas.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? No, there are no additional steps that integrate the claims into a practical application. Although the independent claim 1 recites “f) repeating a) to e) at different times over the course of cancer treatment or after completion thereof to determine the effect of the cancer treatment and/or the maintenance of remission in said subject, wherein the cancer treatment is surgery, radiation therapy, bone marrow transplant, immunotherapy, hormone therapy, crvoablation, or chemotherapy” a cancer treatment is not actually claimed as being administered. Furthermore, the types of cancer treatment being monitored in in said subjects are conventional as demonstrated in the prior art rejections documented below and are not a particular treatment.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No, there are no additional elements that are significantly more than the judicial exceptions.
Regarding claim 6, the claim requires the routine and conventional active steps of enriching the sample for EVs, isolating small nucleic acids, quantitating RE DNAs and repeating steps at different times over the course of treatment or after treatment to determine the effect of treatment and/or the maintenance of remission similar to that of Sansone et al., (“Sansone”; Patent App. Pub. WO 2019236123 A1, Dec. 12, 2019, Filed on Oct. 29, 2018 ).
Sansone discloses methods for detecting cancer and/or the spread of the cancer, and methods for determining the efficacy of a cancer therapy comprising isolating extracellularvesicles (EVs) from a subject and detecting the presence of DNA: RNA hybrids via immunoprecipitation. (Abstract). Thus, the claim does not provide additional steps which are significantly more.
Dependent claims require limitations towards the RE DNAs, sample, subject, cancer, and cancer treatment. which are all routine and conventional based on Sansone et al., (“Sansone”; Patent App. Pub. WO 2019236123 A1, Dec. 12, 2019, Filed on Oct. 29, 2018).
Response to Arguments
Applicant's arguments filed 03/02/2026 (Pg. 8-9) with respect to claims 3, and 6-15 have been fully considered but they are not persuasive. To clarify some instances argued in the response filed 03/02/2026 see responses to each argument made by Applicant below:
Applicants’ argument: “Claim 6 has been amended to include the step of treating the subject. It is respectfully submitted that this limitation imposes a meaningful limit on the judicial exception and integrates the recited judicial exception into a practical application.”
Response: Applicant’s arguments have been fully considered and found unpersuasive because the treatment is of high generality and there is an absence of treating the subject with a particular type of treatment in the claims.
Claim Rejections - 35 USC § 103
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 3, and 6-15 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Sansone et al., (“Sansone”; Patent App. Pub. WO 2019236123 A1, Dec. 12, 2019, Filed on Oct. 29, 2018).
Sansone discloses methods for detecting cancer and/or the spread of the cancer, and methods for determining the efficacy of a cancer therapy comprising isolating extracellular vesicles (EVs) from a subject and detecting the presence of DNA: RNA hybrids via immunoprecipitation. (Abstract).
Regarding claim 6, Sansone teaches a method comprising “a method for evaluating the therapeutic efficacy of a cancer therapy in a subject in need thereof, comprising: a) isolating EVs from a first biological sample obtained from the subject at a first time point and detecting DNA… in the isolated EVs from the first biological sample …; and b) isolating EVs from a second biological sample obtained from the subject following administration of the cancer therapy and detecting DNA… in the isolated EVs from the second biological sample… wherein the cancer therapy is effective when the levels of the DNA… observed in step (b) are reduced compared to the levels of the DNA… observed in step (a).” (Para. 10). Sansone teaches a method comprising “the biological sample comprises… blood” (Para. 16). Sansone teaches a method comprising ” EV-DNA was isolated” (Para. 211). Sansone teaches a method comprising “In some embodiments, the EVs are isolated via density-based isolation… size-based isolation, … or any combination thereof. In some embodiments, the density-based isolation comprises differential centrifugation, and optionally, density gradient centrifugation.” (Para. 14). Sansone teaches a method comprising “Any of the above methods may further comprise performing quantitative assays to detect one or more nucleic acid sequences” (Para. 180). Sansone teaches a method comprising “Alu, telomere and ribosomal DNA quantification… the quantification of Alu and 5s DNA in hybrid and non-hybrid exosomal fractions was conducted by Real Time PCR” (Para. 213). Sansone teaches a method comprising “compared to the average amount of DNA:RNA hybrid complexes in extracellular vesicles obtained from a healthy subject” (Para. 181). Sansone teaches a method comprising “following administration of chemotherapy” (Para. 11) and “following administration of radiotherapy” (Para. 12). “DNA” reads on small nucleic acids. “Alu and 5s DNA” read on repetitive elements. Furthermore, Sansone teaches “Many modifications and variations of this present technology can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatuses within the scope of the present technology, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the present technology. It is to be understood that this present technology is not limited to particular methods, reagents, compounds compositions or biological systems, which can, of course, vary” (Para. 302). Thus, Sansone suggests a method to monitor cancer treatment in a subject diagnosed with cancer, comprising: a) obtaining a blood or serum sample from the subject; b) enriching the sample for EVs, c) isolating small nucleic acids from b);d) quantitating RE DNAs present in c);e) comparing the level of RE DNAs in said sample to the level of RE DNAs in a control wherein the control does not have cancer, wherein an increase in levels of RE DNAs as compared to the control indicates the subject has cancer; and f) repeating a) to e) at different times over the course of cancer treatment or after completion thereof to determine the effect of the cancer treatment and/or the maintenance of remission in said subject, wherein the cancer treatment is surgery, radiation therapy, bone marrow transplant, immunotherapy, hormone therapy, cryoablation, or chemotherapy.
The teachings of Sansone are documented above in the rejection of claim 6 under 35 U.S.C. 103. Claims 3 and 7-15 depends on claim 6.
Regarding claim 3, Sansone teaches a method wherein “Any of the above methods may further comprise performing quantitative assays to detect one or more nucleic acid sequences using direct sequencing, random shotgun sequencing, Sanger polymerase chain reaction (PCR) analysis, sequencing analysis … quantitative PCR…” (Para. 180). Thus, Sansone teaches a method wherein the RE DNAs present in d) are quantitated by PCR and/or sequencing.
Regarding claim 7, Sansone teaches a method wherein “the biological sample comprises… blood” (Para. 16). Thus, Sansone teaches a method wherein the sample is blood.
Regarding claim 8, Sansone teaches a method wherein “isolation of EVs from low volume samples (e.g., about 1-5 µl, about 5-10 µl, about 10-15 µl, about 15-20 µl, or about 20-25 µl)” (Para.153). Furthermore, the MPEP states, "Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." (MPEP 2144.05). Thus, Sansone teaches a method wherein the sample is about 50 µl of blood.
Regarding claim 9, Sansone teaches a method wherein “preferential enrichment of DNA… for satellite sequences (including … Hsatll pericentromeric satellite” (Para. 264). Thus, Sansone teaches a method wherein the repetitive DNA is at least one of HSATI, HSATII, L1P1 or Charlie 3.
Regarding claim 10, Sansone teaches a method wherein “genomic DNA (gDNA) from the sample (e.g., total DNA from extracellular vesicles isolated from a biological sample… DNA:RNA hybrid complexes ” (Para. 158). “gDNA” reads on total nucleic acid sequences. Thus, Sansone teaches a method wherein the RE DNA is quantitated as a proportion of RE DNA sequences to total nucleic acid sequences (including RE DNA, RE RNA non-RE gDNA and non-RE RNA).
Regarding claim 11, Sansone teaches a method wherein “high ratio Hybrid/Non-Hybrid) were ribosomal, purine rich sequences (simple repeats), satellite and endogenous viral sequences” (Para. 263). Thus, Sansone teaches a method wherein the RE DNA is quantitated as a ratio of one or more RE DNA sequences to one or more down-regulated non-RE sequences that co- purify with EVs.
Regarding claim 12, Sansone teaches a method wherein “wherein an increase in the levels of the DNA:RNA hybrid complexes observed in step (b) compared to the levels of the DNA:RNA hybrid complexes observed in step (a) indicates progression of the cancer in the subject” (Para. 8). Sansone also teaches a method wherein “a method for evaluating the therapeutic efficacy of a cancer therapy in a subject in need thereof… following administration of the cancer therapy and detecting DNA:RNA hybrid complexes in the isolated EVs from the second biological sample … wherein the cancer therapy is effective when the levels of the DNA:RNA hybrid complexes observed in step (b) are reduced compared to the levels of the DNA:RNA hybrid complexes observed in step (a)” (Para. 10). Sansone teaches a method wherein “the methods described herein include the administration of a treatment for cancer to a subject who has been identified as having cancer” (Para. 178). Thus, Sansone teaches a method wherein said subject with increased levels of RE DNA is treated for cancer.
Regarding claim 13, Sansone teaches a method wherein “In some embodiments, the cancer is breast cancer, lung cancer, or Burkitt’s lymphoma. In some embodiments, the cancer is associated with hypoxic tumors” (Para. 19). Sansone also teaches a method wherein “a number of cancers” (Para. 5).Thus, Sansone teaches a method wherein the cancer is Central Nervous System Cancers, Adult Ocular and Orbital (Ocular Adnexa) Tumors, Head and Neck Cancer, Thyroid Cancer, Endocrine and Neuroendocrine Tumors, Breast Cancer, Lung Cancer, Esophageal Cancer, Hepatocellular Carcinoma, Pancreatic Cancer, Biliary Tract Cancer, Gastric Cancer, Bladder Cancer, Prostate Cancer, Colorectal Cancer, Anal Cancer, Germ-Cell Cancer of the Testis and Related Neoplasms, Renal Cell Cancer, Ovarian, Fallopian Tube, and Primary Peritoneal Cancer, Uterine Cancer, Cervical Cancer, Carcinoma of the Vagina and Vulva, Gestational Trophoblastic Neoplasia, Non-Melanoma Skin Cancer, Malignant Melanoma, Primary Bone Tumors, Soft Tissue Sarcomas, Leukemias, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, and/or pediatric cancers, including solid tumors such as bone and soft tissue sarcomas, neuronal cancers such as neuroblastoma, brain cancers, B and T-cell leukemias, myeloid leukemias, kidney, liver or eye cancers.
Regarding claim 14, Sansone teaches a method wherein “a number of cancers” (Para. 5). “a number of cancers” read on osteosarcoma. Thus, Sansone teaches a method wherein the cancer is osteosarcoma.
Regarding claim 15, Sansone teaches a method wherein “In some embodiments, the cancer is breast cancer” (Para. 19). Thus, Sansone teaches a method wherein the cancer is breast cancer.
Therefore, the invention as recited in claims 3 and 6-15 are prima facie obvious over the prior art Sansone et al. One of ordinary skill in the art would have had a reasonable expectation of success given the obviousness of the claims. It would have been obvious to provide a method to monitor cancer treatment in a subject diagnosed with cancer according to the limitations of the instant application claims 3 and 6-15 based on Sansone et al. (Patent App. Pub. No. WO 2019236123 A1).
Response to Arguments
Applicant' s arguments filed 03/02/2026 (Pg.9-10) with respect to claim 3. 6-15 and 21 have been considered but are not persuasive. To clarify some instances argued in the response filed 03/02/2026 see responses to each argument made by Applicant below:
Applicants’ argument: “Sansone does not teach or suggest claim 6's isolation of "small nucleic acids" from EVs (step (c))”(Pg. 10)
Response: Applicant's argument filed 03/02/2026 has been fully considered but is not persuasive because, as stated in the revised rejection under 35 U.S.C. 103 (documented above) towards claim 6, Sansone teaches a method comprising ” EV-DNA was isolated” (Para. 211). Furthermore, DNA reads on small nucleic acids.
Applicants’ argument: “does not disclose... (ii) performing claim 6's comparison to "a control wherein the control does not have cancer” (Pg. 10)
Response: Applicant's argument filed 03/02/2026 has been fully considered but is not persuasive because, as stated in the revised rejection under 35 U.S.C. 103 (documented above) towards claims 6, briefly, “compared to… DNA… in extracellular vesicles obtained from a healthy subject” Para. (181).
Applicants’ argument: “Sansone neither provides the motivation to practice the claimed invention nor a reasonable expectation of success.” (Pg. 10)
Response: Applicant's argument filed 03/02/2026 has been fully considered but is not persuasive because, the claim elements were known in the art and one of skill in the art could have provided the method, as suggested in the 35 U.S.C. 103 rejection above, with a reasonable expectation of success.
Conclusion of Response to Arguments
In view of the amendments, documented above in this Final Office Action are revised rejections as well as responses to arguments. No claims are in condition for allowance.
Conclusion
THIS ACTION IS MADE FINAL. 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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/KENDRA R VANN-OJUEKAIYE/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682