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 .
The amendment filed 24 February 2026 has been received, entered and considered. The following information has been made of record in the instant amendment:
1. Claim 2 has been canceled.
2. New Claim 11 has been added.
3. Claim 1 has been amended.
4. Remarks drawn to rejections under 35 USC 102, 103 and double patenting.
The following objection(s)/rejection(s) has/have been overcome:
The rejection of Claim(s) 1, 3, 6 and 8 under 35 U.S.C. 102(a)(1) as being anticipated by Yukawa et al (Bio Industry, 2015, 32(11), 15-19, Machine translation; cited in IDS filed 04/28/2021; newly cited in this rejection) has been withdrawn in view of the amendment to claim 1. Yukawa does not expressly teach cleaning the device that captured the extracellular vesicle as in amended claim 1.
The rejection of Claim(s) 4-7 under 35 U.S.C. 103 as being unpatentable over Yukawa et al (Bio Industry, 2015, 32(11), 15-19, Machine translation; cited in IDS filed 04/28/2021; newly cited in this rejection) has been withdrawn in view of the amendment to claim 1.
Claims 1 and 3-11 are pending in the case. Claim 10 has been withdrawn from consideration. Claims 1, 3-9 and 11 are under prosecution.
The following rejections are necessitated by Applicant's amendment filed 24 February 2026 wherein the limitation in pending claim 1 has been amended.
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.
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.
Claim(s) 1, 3-9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Yukawa et al (Bio Industry, 2015, 32(11), 15-19, Machine translation; cited in IDS filed 04/28/2021; of record) in view of Michael et al (Oral Dis., 2010, 16(1), 34-38; cited in IDS filed o4/28/2021; of record).
Yukawa et al teaches recovery of exosomes from HepG2 cell culture supernatant as a sample by capturing exosomes via contact with a nanowire device. The exosomes were trapped in the voids of the nanowires (page 17, part 3 (the first page of the English translation is considered page 15); limitation of claim 1-step 1 and limitation of claim 6-nanowires). The miRNA was extracted by adding a disruption solution (page 18, part 4; step 3 in claim 1). The nanowire device of Yukawa is made from a material that is resistant to the disruption solution (PMMA device; page 17, third full para under the sub-heading for part 3; limitation of claim 3). Yukawa also teaches that its method can be used for extracting miRNA from urine samples, which is a non-invasive biological sample solution (page 19, line 3; limitation of claim 8). In addition, the void where the exosomes are trapped could also be detected when stained with red fluorescence (page 17, part 3, last para).
Yukawa does not expressly teach the use of cellulose fibers as in claims 4-7. Since the nanowire material captures the exosomes in the voids one of ordinary skill in the art will recognize that the same trapping of the exosomes can also be done with a nanowire fabric like cellulose nanofiber as in claims 4-7 with a reasonable expectation of success.
Yukawa does not teach that the sample solution is saliva as in claim 9.
Michael teaches a method of isolating exosomes from saliva. After isolation the exosome was washed with PBS then lysed to extract miRNA (Abstract; page 2, last para; page 3, second para; page 3, para under sub-title: Salivary exosome isolation; cleaning as in claim 1 and saliva as in claim 9). Even though Michael teaches centrifugation method one of ordinary skill in the art will apply the washing step taught by Michael in the method of Yukawa for cleaning the device in order to get a purified exosome sample for miRNA extraction.
Even though Yukawa does not teach the device cleaning step as in claim 1, it teaches recovery of exosomes from HepG2 cell culture supernatant as a sample by capturing exosomes via contact with a nanowire device. The exosomes were trapped in the voids of the nanowires. The miRNA was extracted by adding a disruption solution. The nanowire device of Yukawa is made from a material that is resistant to the disruption solution. Yukawa also teaches that its method can be used for extracting miRNA from urine samples, which is a non-invasive biological sample solution. Since the nanowire device of Yukawa is resistant to the disruption solution, and it traps the exosomes in the voids, one of ordinary skill in the art will recognize that after the exosomes are trapped in the nanowire voids, the nanowire with the trapped exosomes can be immersed in the PBS solution as taught by Michael and cleaned, and then the device can be brought in contact with the disruption solution to extract the miRNA. This is well within the skill level of the artisan to recognize this modification and perform with a reasonable expectation of success.
One of ordinary skill in the art will recognize that the nanowire which is the device that captured the exosomes can be immersed in PBS to clean the device and then immersed the cleaned device in the disruption solution to extract miRNA as in claims 1 and 11.
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.'" KSR, 550 U.S. at, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
According to the rationale discussed in KSR above, the rationale in (G) above is seen to be applicable here since based on the prior art teachings saliva sample solution can be used for isolating exosomes and miRNA from the exosomes. One of ordinary skill in the art will also recognize that the cleaning of the device that captured the exosomes between the extracellular vesicle capture step and the miRNA extraction as in claim 1 can be done based on the teachings of Yukawa with a reasonable expectation of success.
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the combined teachings of the prior art. Method improvement is the motivation. Yukawa teaches that the centrifugation method requires several tens of mL of sample, a separation time of 4 to 5 hours and a low recovery rate, which makes it a complicated method (page 17, second para in part 3). This provides the motivation to use the method of Yukawa to isolate miRNA from extracellular vesicles and also use saliva as a sample solution and perform the cleaning step as claimed in order to get pure exosomes and then isolate highly pure miRNA. One of ordinary skill in the art would be motivated to use the cellulose fibers as in the instant claims since cellulose is a natural material which is readily available and is ecofriendly.
Response to Applicant’s Remarks
Applicant has traversed the rejection of claims under 35 USC 103 arguing that the Office acknowledges that Yukawa does not teach the device cleaning step of claim 2, but contends that Michael supplements Yukawa by teaching the step of washing the exosomes with PBS and then lysing to extract miRNA. Michael’s method includes performing an ultracentrifugation step to obtain a pellet containing exosomes, washing the pellets with PBS and then subjecting to ultracentrifugation again, and lysing the sample exosomes to obtain exosomal RNA. The skilled artisan would have realized that Michael’s washing step is limited only to the pellet. Michael does not and cannot extend its washing step to be applied to the entire ultracentrifugation device.
The present invention is distinguishable from Michael because the “immersing the device in a cleaning solution” step is not taught by Michael. For the above reasons claims 1 and 3-9 are patentable over the cited references (Remarks-pages 4-6).
Applicant’s arguments have been considered but are not found to be persuasive. It has been acknowledged in the rejection that Michael teaches centrifugation. However, Michael uses PBS for washing the pellets of exosomes.
Yukawa et al teaches recovery of exosomes from HepG2 cell culture supernatant as a sample by capturing exosomes via contact with a nanowire device. The exosomes were trapped in the voids of the nanowires. The miRNA was extracted by adding a disruption solution. The nanowire device of Yukawa is made from a material that is resistant to the disruption solution. Yukawa also teaches that its method can be used for extracting miRNA from urine samples, which is a non-invasive biological sample solution. Since the nanowire device of Yukawa is resistant to the disruption solution, and it traps the exosomes in the voids, one of ordinary skill in the art will recognize that after the exosomes are trapped in the nanowire voids, the nanowire with the trapped exosomes can be immersed in the PBS solution as taught by Michael and then the device can be brought in contact with the disruption solution to extract the miRNA. This is well within the skill level of the artisan to recognize this modification and perform with a reasonable expectation of success. Therefore, the combined teachings of the prior art renders amended claim 1, and dependent claims 3-9 and 11 obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
The USPTO Internet website contains Terminal Disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3, 6 and 8 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-6, 10-12 and 18 of U.S. Patent No. 11,845,975 (‘975) in view of Yukawa et al (Bio Industry, 2015, 32(11), 15-19, Machine translation; cited in IDS filed 04/28/2021; of record and newly cited) and further in view of Michael et al (Oral Dis., 2010, 16(1), 34-38; cited in IDS filed o4/28/2021; of record and newly cited). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant Claim 1 is drawn to a method of extracting miRNA from extracellular vesicles in a sample solution by bring the solution into contact with a device to capture the extracellular vesicle in the device, a device cleaning comprising cleaning the device that captured the extracellular vesicle by immersing the device in a cleaning solution, and bringing the vesicle in contact with a disruption solution and extracting the miRNA. Dependent claims 3, 6 and 8 recite limitations drawn to the device formed of a material which is resistant to the disruption solution, the device being nanowires, and the sample solution being a non-invasive biological sample solution.
Claim 1 of ‘975 is drawn to a method comprising providing a urine sample and enriching miR-16-1-3p in the sample using a nanowire. Dependent claims 2-6, 10-12 and 18 of ‘975 recite limitations drawn to the type of miRNA’s, extracting a second miRNA, collecting extracellular vesicles from the nanowire, wherein the extracellular vesicles comprise exosomes, and microvesicles, enriching at least one additional nucleic acid from the urine or urine extract.
The teachings of Yukawa and Michael are set forth above. Yukawa et al teaches recovery of exosomes from HepG2 cell culture supernatant as a sample by capturing exosomes via contact with a nanowire device. The exosomes were trapped in the voids of the nanowires. The miRNA was extracted by adding a disruption solution. The nanowire device of Yukawa is made from a material that is resistant to the disruption solution. Yukawa also teaches that its method can be used for extracting miRNA from urine samples, which is a non-invasive biological sample solution. Since the nanowire device of Yukawa is resistant to the disruption solution, and it traps the exosomes in the voids, one of ordinary skill in the art will recognize that after the exosomes are trapped in the nanowire voids, the nanowire with the trapped exosomes can be immersed in the PBS solution as taught by Michael and cleaned, and then the device can be brought in contact with the disruption solution to extract the miRNA. This is well within the skill level of the artisan to recognize this modification and perform with a reasonable expectation of success.
Claims 1, 2-6, 10-12 and 18 of ‘975 differ from the instant claims in that the instant claims are drawn to extraction of miRNA in general, and inclusion of a device cleaning step wherein the device that captured the extracellular vesicle by immersing the device in a cleaning solution, whereas the method of ‘975 is drawn to extracting specific miRNA. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention that the method of ‘975 could be successfully employed for extracting miRNA as in the instant method in view of Yukawa and Michael.
In the instant case ‘975 teaches the capture and extraction of miRNA using nanowires applicant claims. Although the claims of '975 extract some specific miRNA’s, one of ordinary skill in the art would readily recognize that the scheme taught by '975 could be employed for extracting miRNA as claimed with a reasonable expectation of success in view of Yukawa and Michael. The use of known devices and reagents in a method of extraction of miRNA taught in the prior art is not seen to render the instantly claimed method unobvious over the art. Once the general scheme has been shown to be old, the burden is on the applicant to present reason or authority for believing that extraction of some specific miRNA would not render the instant method of extracting miRNA obvious.
Response to Applicant’s Remarks
Applicant has traversed the rejection of claims 1, 3 and 8 on the ground of non-statutory obviousness-type double patenting over claims 1-6, 10-12 and 18 of US Patent No. 11,845,975 arguing that amended claim 1 recites “a device cleaning comprising cleaning the device that captured the extracellular vesicle by immersing the device in a cleaning solution.” This is described in original claim 2 and para 0020 of the as-filed specification.
None of the claims in the ‘975 patent is directed to a device cleaning step. It appears that the Office also tacitly acknowledges this distinction, as original claim 2 is not subject to double patenting rejection based on the ‘975 patent. Accordingly pending claims 1 and 3-9 of the present application are patentably distinct from the claims of the ‘975 patent (Remarks-page 6).
In view of Applicant’s remarks, the obviousness-type double patenting rejection as set forth above is made of record.
Claims 1 and 3-9 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 11-14 of U.S. Patent No. 12,038,360 (‘360) in view of Yukawa et al (Bio Industry, 2015, 32(11), 15-19, Machine translation; cited in IDS filed 04/28/2021; of record) in view of Michael et al (Oral Dis., 2010, 16(1), 34-38; cited in IDS filed o4/28/2021; of record). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant Claim 1 is drawn to a method of extracting miRNA from extracellular vesicles in a sample solution by bring the solution into contact with a device to capture the extracellular vesicle in the device, a device cleaning comprising cleaning the device that captured the extracellular vesicle by immersing the device in a cleaning solution, and bringing the vesicle in contact with a disruption solution and extracting the miRNA. Dependent claims 3 and 8 recite limitations drawn to the device formed of a material which is resistant to the disruption solution, and the sample solution being a non-invasive biological sample solution.
Claim 11 of ‘360 is drawn to a method of extracting miRNA from extracellular vesicles by bring a sample solution into contact with a device to capture the extracellular vesicle and then extracting the miRNA from the captured vesicle wherein the device is a nanostructure body made of cellulose nanofibers. Dependent claims 12-14 recite limitations drawn to confinement of the vesicle in the nanopore of the device, the sample solution being a non-invasive sample solution and wherein the sample solution is saliva.
Claims 11-14 of ‘360 differ from the instant claims in that the instant claims are drawn to extraction of miRNA by bringing a disruption solution in contact with the vesicles and inclusion of a device cleaning step wherein the device that captured the extracellular vesicle by immersing the device in a cleaning solution, whereas the claim of ‘360 recites extracting miRNA from the vesicles. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention that the method of ‘360 could be successfully employed for extracting miRNA in view of Yukawa and Michael.
Yukawa teaches the use of disruption solution for extracting miRNA in its method which uses nanowires for capturing exosomes (see Yukawa’s teaching as above). Michael et al teaches extraction of miRNA from exosomes obtained from saliva sample.
In the instant case ‘360 teaches the capture and extraction of miRNA using cellulose nanowires applicant claims. Although the claims of '360 does not specifically recite adding a disrupting solution to contact the vesicles and the device cleaning step, and one of ordinary skill in the art would readily recognize that the scheme taught by '360 could be employed for extracting miRNA as claimed with a reasonable expectation of success in view of Yukawa and Michael. Yukawa et al teaches recovery of exosomes from HepG2 cell culture supernatant as a sample by capturing exosomes via contact with a nanowire device. The exosomes were trapped in the voids of the nanowires. The miRNA was extracted by adding a disruption solution. The nanowire device of Yukawa is made from a material that is resistant to the disruption solution. Yukawa also teaches that its method can be used for extracting miRNA from urine samples, which is a non-invasive biological sample solution. Since the nanowire device of Yukawa is resistant to the disruption solution, and it traps the exosomes in the voids, one of ordinary skill in the art will recognize that after the exosomes are trapped in the nanowire voids, the nanowire with the trapped exosomes can be immersed in the PBS solution as taught by Michael and cleaned, and then the device can be brought in contact with the disruption solution to extract the miRNA. This is well within the skill level of the artisan to recognize this modification and perform with a reasonable expectation of success.
The use of known devices and reagents in a method of extraction of miRNA taught in the prior art is not seen to render the instantly claimed method unobvious over the art. Once the general scheme has been shown to be old, the burden is on the applicant to present reason or authority for believing that the method of extraction taught by the prior art would not render the instant method of extracting miRNA obvious.
Response to Applicant’s Remarks
Applicant has traversed the rejection of claims 1 and 3-9 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 11-14 of U.S. Patent No. 12,038,360 (‘360) in view of Yukawa et al (Bio Industry, 2015, 32(11), 15-19, Machine translation; cited in IDS filed 04/28/2021; of record) in view of Michael et al (Oral Dis., 2010, 16(1), 34-38; cited in IDS filed o4/28/2021; of record) arguing that amended claim 1 recites “a device cleaning comprising cleaning the device that captured the extracellular vesicle by immersing the device in a cleaning solution.” This is described in original claim 2 and para 0020 of the as-filed specification.
None of the claims in the ‘360 patent is directed to a device cleaning step. It appears that the Office also tacitly acknowledges this distinction, as original claim 2 is not subject to double patenting rejection based on the ‘360 patent. Accordingly pending claims 1 and 3-9 of the present application are patentably distinct from the claims of the ‘360 patent (Remarks-page 7).
Applicant’s arguments have been considered but are not found to be persuasive. As set forth above the instant claims are rendered obvious over those of the ‘360 patent in view of Yukawa and Michael.
Conclusion
Elected claims 1, 3-9, and 11 (Group I) are rejected.
Claim 2 has been canceled.
Claim 10 (Group II) is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim.
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/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693
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