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 .
Election/Restrictions
Applicant’s election without traverse of claims 12, 14-19 in the reply filed on 22 May 2026 is acknowledged.
Claims 1-9, 13, and 24-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 22 May 2026.
Information Disclosure Statement
The information disclosure statement(s) (IDS) file 13 June 2024, 2 August 2024, 2 October 2024, 28 January 2025, 21 March 2025, 2 April 2025, 9 January 2026, and 22 May 2026 are considered, initialed, and attached hereto.
The listing of references in the specification (on pages 32-33) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or in a proper IDS, they have not been considered.
Claim Status
Claims 1-9, 12-19, and 23-30 are currently pending.
Claims 1-9, 13, and 24-30 are withdrawn per Election/Restriction section above.
Claims 10-11 and 20-22 are canceled.
Claims 12, 14-19, and 23 are under examination.
Specification
The abstract of the disclosure is objected to because it contains a second paragraph reciting, in smaller text, what appears to be a file name: “24366296.docx”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities: page 30, Example 5, second paragraph, third line recites “FIGs. 4B-4G”. However, in the filed drawings, FIG. 4 only contains views 4A and 4B. Based on the references to FIGs. 5B-D and 5E-G in the related, preceding paragraph, Examiner suggests that this recitation of “FIGs. 4B-4G” was intended to read “FIGs. 5B-5G”.
Appropriate correction is required.
The use of terms including, but not limited to, Amicon, NanoSight, NanoDrop, mirVana, and TaqMan, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim objected to because of the following informalities: the recitation "EV markers" on line 2 should read "EV tumor markers". Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) - Indefiniteness
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 12, 14-19, and 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 12 recites the limitation "the quantitative colocalization of EV marker(s) and drug-resistance biomarker(s)" in lines 10-11. There is insufficient antecedent basis for this limitation in the claim because the colocalization of EV marker(s) and drug-resistance biomarker(s) earlier in the claim is not described as being quantitative. Claims 14-19 and 23 are also rejected based on their dependency on claim 12. Examiner notes that claim 19 recites “the quantification of the colocalization” in lines 1-2, which requires the limitation in question for its antecedent basis. For the purpose of examination, claim 12 step (c) of determining colocalization is interpreted as requiring determining quantitative colocalization to provide antecedent basis for the limitation in question in claim 12 as well as for the similar recitation in claim 19.
Claim 16 recites the limitation "the antibodies or antigen binding portions thereof that bind to EV tumor markers" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. For the purpose of examination, this is interpreted as requiring that the EV tumor markers are bound by an antibody or antigen binding portion thereof.
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 12, 14-19, and 23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. While the claims are directed to a process, and therefore meet step 1 of the subject matter eligibility test (see MPEP §2106.03), the claim(s) recite(s) the abstract idea, which is a mental process because it can be done in the human mind looking at data (quantitative or qualitative) of colocalization from before and after the chemotherapy treatment.
Step 2A of the subject matter eligibility test require a two-pronged analysis. Prong One asks: does the claim recite an abstract idea, law of nature or natural phenomenon? As discussed in MPEP §2106.04(II)(A)(1), the meaning of “recites” is “set forth” or “describes”. That is, a claim recites a judicial exception when the judicial exception is “set forth” or “described” in the claim. In the instant case, the claims describe abstract ideas of detecting changes in colocalization of markers.
Prong Two of the analysis under step 2A asks: does the claim recite additional elements that integrate the judicial exception into a practical application of the judicial exception? As discussed in MPEP §2106.04(II)(A)(2):
Because a judicial exception is not eligible subject matter, Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"); Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016) (eligibility "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself."). For a claim reciting a judicial exception to be eligible, the additional elements (if any) in the claim must "transform the nature of the claim" into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981, either at Prong Two or in Step 2B.
The considerations to be used are set forth in MPEP §2106.04(d)(2) and MPEP §2106.05(a) through (c) and (e) through (h). Turning to those sections of the MPEP:
MPEP §2106.05(a) has to do with improvements to the functioning of a computer or to any other technology or technical field. The claims at issue do not improve the functioning of a computer or the technical field of extracellular vesicle (EV) detection.
MPEP §2106.05(b) has to do with whether the claims involve the use of a particular machine. In this case, the claims do not involve the use of a particular machine as all materials used in steps of the method are described generically.
MPEP §2106.05(c) has to do with whether the claims involve a particular transformation. Here, the claims do not involve a particular transformation because the claims are for a process.
MPEP §2106.05(e) has to do with “other meaningful limitations”. The additional limitations imposed upon the abstract ideas consist of providing a sample, isolating tumor-derived EVs (tEVs) from the sample that are double labeled with EV tumor markers and drug-resistance markers, and determining colocalization of EV tumor markers and drug-resistance biomarkers (claim 12); using a plasmon-enhanced EV detection method (claim 14); selecting tEVs by a marker panel comprising EpCAM, EGFR, MUC1, or HER2 (claim 15); wherein the EV tumor markers comprising fluorescent dyes (claim 16); wherein the drug-resistance biomarkers comprise protein or RNA (claim 17); wherein the drug-resistance biomarkers are P-gp and surviving (claim 18), wherein the markers are analyzed using multichannel fluorescence imaging in a single EV (claim 19); and recommending, prescribing, and/or administering a therapeutically effective amount of a chemotherapy to a subject. These are not meaningful limitations because they generally link the use of the judicial exceptions to the particular technological environment of EV analysis.
MPEP §2106.04(d)(2) has to do with whether the additional elements apply or use the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. While the recited step of “recommending, prescribing and/or administering a therapeutically effective amount of a chemotherapy to a subject” is a treatment, it is not considered particular because (1) a therapeutically effective amount of a chemotherapy as recited is a generic treatment for cancer and (2) the treatment provided has no more than a nominal or insignificant relationship to the judicial exception as it is not limited in any manner by the abstract idea of detecting changes in colocalization.
MPEP §2016.05(f) raises the question as to whether the additional elements recited in the claim represent “mere instructions to apply an exception”. As the additional limitations discussed above regarding claims 12 and 14-19 merely describe how the data that is used in the abstract idea is gathered, the additional elements represent mere instructions to apply the exceptions.
MPEP §2106.05(g) has to do with whether the additional elements of the claim amount of insignificant extra-solution activity. MPEP §2106.05(g) notes that “[d]etermining the level of a biomarker in blood” is an example of “mere data gathering” which the courts have found to be insignificant extra-solution activity. The additional limitations discussed above regarding claims 12 and 14-19 similarly determine the presence of biomarkers in a sample (the colocalization of two markers itself is considered a biomarker) represent mere gathering of the colocalization data used in the abstract idea of detecting changes in colocalization.
MPEP §2106.05(h) has to do with whether the additional elements amount to more than generally linking the use of a judicial exception to a particular technological environment or field of use. The recitation of the judicial exceptions being applied to colocalization of markers on extracellular vesicles and monitoring drug-resistances longitudinally in a subject having cancer represent “field of use” limitations. However, as MPEP §2106.05(h) indicates, such limiting to a particular “field of use” does not confer patentability to otherwise ineligible subject matter.
In addition, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception (as set forth in step 2B of the subject matter eligibility test) because determining biomarker colocalization and the specific marker panel for selecting tEVs were known in the prior art as seen in Zhong et al. (US Patent Document Cite No. 12 in IDS filed 13 June 2024, see 35 U.S.C. 103 rejection of claims 12 and 15 below), determining drug resistance using EV biomarkers P-gp and survivin was known in the art as seen in Pompili et al. (“Extracellular Vesicles and Resistance to Anticancer Drugs: A Tumor Skeleton Key for Unhinging Chemotherapies” Front Oncol 12, 933675 (2022), see 35 U.S.C. 103 rejection of claim 18 below).
Having considered the factors discussed in MPEP §2106.05 as well as the prior art of Zhong et al. and Pompili et al., it is clear that the additional elements recited in the claims, whether considered individually or as a combination, do not integrate the judicial exceptions into a practical application of those exceptions in such a way as to provide meaningful limits on the use of the judicial exception and do not amount to significantly more than the judicial exception. Therefore, claims 12, 14-19, and 23 are rejected here under 35 U.S.C. 101.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 12, 15-17, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (US Patent Document Cite No. 12 in IDS filed 13 June 2024)(US 2019/0310172, published 10 October 2019, effectively filed 5 April 2018), herein Zhong, in view of Cheresh et al. (US 2018/0203014, published 19 July 2018, effectively filed 20 April 2015), herein Cheresh, and in view of Kato et al. (“Serum exosomal P-glycoprotein is a potential marker to diagnose docetaxel resistance and select a taxoid for patients with prostate cancer” Urol Oncol 33(9), 385.e15 - 385.e20 (2015)), herein Kato.
Regarding claim 12, Zhong teaches a method for characterizing extracellular vesicles (EVs) ([0042]; FIG. 1D) comprising: providing a sample from a subject (“The compositions and methods of the invention can be used to assess any useful biomarkers in a biological sample for charactering a phenotype associated with the sample” [0037]), isolating tumor-derived EVs (tEVs) from the sample (“Any one or more of […] disease biomarkers (141) […] is used to capture a microvesicle population” [0042]; “In various embodiments, the disease or disorder comprises a cancer” [0014]; FIG. 1D element 141 is the capture/isolation of the EVs using a disease biomarker) and double labeling the tEVs with an additional detection biomarker that provides information about tumor (“Thereafter, any one or more of […] disease biomarkers (144) […] is used to detect the captured microvesicle population” [0042]; FIG. 1D element 144 is the detection of disease biomarkers on the isolated/captured EVs). As the detection happens on the captured EVs, the detection and capture markers necessarily colocalize to the same EVs. However, Zhong does not teach the method wherein the sample is acquired from multiple time points during treatment with chemotherapy for the purpose of monitoring drug-resistance longitudinally in a subject having cancer, that the additional biomarker of the double labeling is a drug-resistance biomarker, or that the method further comprises detecting changes in the colocalization of EV tumor markers and drug-resistance biomarkers before and after the chemotherapy treatment to determine drug-resistance in the subject. These deficiencies are made up for in the teachings of Cheresh and Kato.
Regarding claim 12, Cheresh teaches a method for monitoring drug-resistance longitudinally in a subject having cancer (“assessing a drug resistance in a tumor or a cancer cell, comprises detecting the presence of a β3 integrin in two samples taken at two different time points [0043]), the method comprising: providing a sample from the subject, where the sample is acquired from the same subject at multiple timepoints (“two samples taken at two different time points” [0043]); isolating EVs and detecting the presence of a drug-resistance biomarker on the EVs (“detecting the presence of a β3 integrin in or on the cancer cell-derived EV” [0043]); and detecting changes in the detection of the drug-resistance biomarker on the EVs from different time points of the sample, thereby determining drug-resistance in the subject based on the quantitative changes (“wherein an increase in β3 integrin in a later sample is diagnostic of development or worsening of a drug resistance […] by detecting the presence of a β3 integrin-expressing EV or CTC, the methods detect the presence of a receptor tyrosine kinase inhibitor resistant cell, e.g., a cancer or a cancer stem cell” [0043]). By combining the teachings of Zhong and Cheresh, one of ordinary skill in the art would arrive at a version of Zhong’s method of isolating vesicles using tumor-specific biomarkers modified by Cheresh’s teachings of using a sample from multiple time points for monitoring drug resistance and using a drug-resistance biomarker in place of Zhong’s additional detection biomarker, and detecting changes in the detection of the drug-resistances biomarker as taught by Cheresh would necessarily detect changes in the colocalization of the tumor-specific biomarker and the drug-resistance biomarker because all EVs captured are labeled by the tumor-specific biomarker. However, the combination of Zhong and Cheresh does not teach a method where the time points the sample is acquired at are during treatment with a chemotherapy. This deficiency is made up for in the teachings of Kato.
Regarding claim 12, Kato teaches that P-gp is a biomarker for docetaxel-resistance (“The results showed that the P-gp level in exosomes isolated from the serum was relatively higher in patients who were docetaxel-resistant than in therapy-naïve patients” page 385.e19 right column paragraph 3; “Our results suggest that detection of P-gp in blood exosomes, which is involved in resistance to docetaxel but not to cabazitaxel, could be useful to diagnose docetaxel resistance and select an appropriate taxoid for patients with CRPC—docetaxel or cabazitaxel” page 385.e19 right column paragraph 4; “Docetaxel is used as the first-line chemotherapy” Abstract). By substituting P-gp and docetaxel for β3 integrin and receptor tyrosine kinase inhibitor in the method of the combination of Zhong and Cheresh, all limitations of claim 12 are taught by the combination of Zhong, Cheresh, and Kato.
Regarding claim 15, the combination of Zhong, Cheresh, and Kato teach the method of claim 12 (see 35 U.S.C. 103 rejection of claim 12 above), and Zhong further teaches that the tEVs are selected by a marker panel comprising EpCAM, EGFR, MUC1, and/or HER2 (“a capture agent for a […] cancer related antigen, including without limitation EpCam, […] and EGFR” [0092]; due to the use of “or” in the claim, the teaching of any one or more of EpCAM, EGFR, MUC1, and HER2 read on the claim).
Regarding claim 16, the combination of Zhong, Cheresh, and Kato teach the method of claim 12 (see 35 U.S.C. 103 rejection of claim 12 above), and Zhong further teaches the method using EV tumor markers that further comprise fluorescent dyes (“In some embodiments, a vesicle is assessed using capture and detection agents that recognize the same vesicle biomarker” [0183], teaching using a detection agent for the same cancer biomarker as the capture agent; “the captured vesicles are detected using fluorescently labeled binding agent (detection agent) against vesicle antigens of interest” [0039]).
Regarding claim 17, the combination of Zhong, Cheresh, and Kato teach the method of claim 12 (see 35 U.S.C. 103 rejection of claim 12 above), and Kato further teaches that the drug-resistance biomarker comprises protein (“Expression of P-gp in exosomes isolated from blood of patients with prostate cancer […] exosomes were subjected to Western blot analysis for P-gp” Fig. 4 legend page 385.e19).
Regarding claim 23, the combination of Zhong, Cheresh, and Kato teach the method of claim 12 (see 35 U.S.C. 103 rejection of claim 12 above), and Kato further teaches the recommending, prescribing and/or administering a therapeutically effective amount of a chemotherapy to a subject “Our results suggest that detection of P-gp in blood exosomes, which is involved in resistance to docetaxel but not to cabazitaxel, could be useful to diagnose docetaxel resistance and select an appropriate taxoid for patients with CRPC—docetaxel or cabazitaxel” page 385.e19 right column paragraph 4). Examiner further notes that claim 23 is not limited to recommending, prescribing, and/or administering the chemotherapy to the subject of the method, but to “a subject” (emphasis added) and thus does not materially limit the method of claim 12 upon which it depends.
One of ordinary skill in the art would be motivated to combine the method of Zhong with the method of Cheresh in order to improve the method of Zhong with the ability to detect drug-resistance in a cancer patient, specifically resistance to receptor tyrosine kinase inhibitors (MPEP §2143 I. G.). If viewed alternatively as the teachings of Zhong being used to improve the method of Cheresh, one of ordinary skill in the art would also be motivative to make this combination because Zhong teaches that their method provides the advantage of improved precipitation selectivity (“In summary, we have developed a plasma EV enrichment method with improved precipitation selectivity” Zhong [0004]). One of ordinary skill in the art would have a reasonable expectation of success in this combination because assaying samples from multiple time points and using a specific drug-resistance marker as the additional detection biomarker in the method of Zhong would not prevent the method from functioning and because precipitating the vesicles using Zhong’s capture agent would not prevent the detection of a β3 integrin as taught by Cheresh. Therefore, the combination of the methods of Zhong and Cheresh would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to perform the simple substitution of β3 integrin as the drug-resistance biomarker and receptor tyrosine kinase inhibitor as the drug as taught by Cheresh in the combination of Zhong and Cheresh with P-gp as the drug-resistance biomarker and docetaxel, a type of chemotherapy, as the drug as taught by Kato (MPEP §2143 I. B.). One of ordinary skill in the art could have performed this substitution and would have found the results of this substitution predictable because it merely exchanges one drug-resistance biomarker and drug pair for another and both pairs of drug-resistance biomarker and drug are shown to have drug-resistance biomarkers that are able to be detected in extracellular vesicles. Therefore, the invention as a whole of claims 12, 15-17, and 23 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claims 14 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (US Patent Document Cite No. 12 in IDS filed 13 June 2024)(US 2019/0310172, published 10 October 2019, effectively filed 5 April 2018), herein Zhong, in view of Cheresh et al. (US 2018/0203014, published 19 July 2018, effectively filed 20 April 2015), herein Cheresh, and in view of Kato et al. (“Serum exosomal P-glycoprotein is a potential marker to diagnose docetaxel resistance and select a taxoid for patients with prostate cancer” Urol Oncol 33(9), 385.e15 - 385.e20 (2015)), herein Kato, as applied to claims 12, 15-17, and 23 above, and further in view of Min et al. (Other Document Cite No. 63 in IDS filed 13 June 2024)(“Plasmon-Enhanced Biosensing for Multiplexed Profiling of Extracellular Vesicles” Adv Biosyst 4(12), e2000003 (2020)), herein Min.
Regarding claim 14, the combination of Zhong, Cheresh, and Kato teach the method of claim 12 (see 35 U.S.C. 103 rejection of claim 12 above). However, none of Zhong, Cheresh, and Kato teach using a plasmon-enhanced EV detection method.
Regarding claim 14, Min teaches a method of capturing and analyzing EVs using a plasmon-enhanced EV detection method (“we implement plasmon-enhanced fluorescence detection, which can amplify fluorescence signals using plasmonic metallic nanostructures, for sensitive, multi-channel EV biomarker profiling” page 2 left column paragraph 2).
Regarding claim 19, Min teaches analyzing biomarkers on EVs using multichannel fluorescence imaging in a single EV (“we report a next-generation nPLEX assay that enables multiplexed single EV analysis of target membrane and intravesicular markers with improved sensitivities. Specifically, […] multi-channel EV biomarker profiling” page 2 left column paragraph 2).
One of ordinary skill in the art would be motivated to combine the method of the combination of Zhong, Cheresh, and Kato with the teachings of Min in order to improve the method with improved sensitivity and multiplexing ability at the level of single EVs as taught by Min (MPEP §2143 I. G.). One of ordinary skill in the art would have a reasonable expectation of success in this combination because Min teaches applying their method to EVs captured via affinity ligands (“We first capture EVs on the Au nanohole surface via affinity ligands” Min page 2 left column paragraph 3), which are equivalent to the capture agents of Zhong. Therefore, the invention as a whole of claims 14 and 19 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claims 18 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (US Patent Document Cite No. 12 in IDS filed 13 June 2024)(US 2019/0310172, published 10 October 2019, effectively filed 5 April 2018), herein Zhong, in view of Cheresh et al. (US 2018/0203014, published 19 July 2018, effectively filed 20 April 2015), herein Cheresh, and in view of Kato et al. (“Serum exosomal P-glycoprotein is a potential marker to diagnose docetaxel resistance and select a taxoid for patients with prostate cancer” Urol Oncol 33(9), 385.e15 - 385.e20 (2015)), herein Kato, as applied to claims 12, 15-17, and 23 above, and further in view of Pompili et al. (“Extracellular Vesicles and Resistance to Anticancer Drugs: A Tumor Skeleton Key for Unhinging Chemotherapies” Front Oncol 12, 933675 (2022)), herein Pompili.
Regarding claim 18, the combination of Zhong, Cheresh, and Kato teach the method of claim 12 (see 35 U.S.C. 103 rejection of claim 12 above), and Kato further teaches that the drug-resistance biomarker is P-gp. However, none of Zhong, Cheresh, and Kato teach using survivin in combination with P-gp as the drug-resistance biomarkers. This deficiency is made up for in the teachings of Pompili.
Regarding claim 18, Pompili teaches that both P-gp and Survivin expression in EVs is associated with resistances to the chemotherapy drugs docetaxel and paclitaxel (Table 4 page 10).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to perform the simple substitution of P-gp as the drug-resistance biomarker and doxetaxel as the drug as taught by Kato in the combination of Zhong, Cheresh, and Kato with both P-gp and survivin as the drug-resistance biomarkers as taught by Pompili in order to gain the advantage of being able to detect resistances to both docetaxel and paclitaxel (MPEP §2143 I. B. and G.). One of ordinary skill in the art could have performed this substitution and would have found the results of this substitution predictable because it merely exchanges one drug-resistance biomarker and drug pair for another and both pairs of drug-resistance biomarker and drug are shown to have drug-resistance biomarkers that are able to be detected in extracellular vesicles. Therefore, the invention as a whole of claim 18 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Conclusion
Claims 12, 14-19, and 23 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jeffrey Lawrence Bellah whose telephone number is (571)272-1024. The examiner can normally be reached M-Th, 7:30-5 ET.
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/JEFFREY BELLAH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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