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 .
Claim Status
Claims 1-10 are pending:
Claims 1-10 are rejected.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. JP 2021-089877, filed on 05/28/2021.
Claim Rejections - 35 USC § 112
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 1-10 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. Dependent claims are hereby rejected due to their dependency from rejected claim 1.
Claim 1 recites “a concentrate”; it is unclear if the concentrate is referring to the first concentrate, second concentrate or a different concentrate. The examiner suggests amending to – a final concentrate – for clarity and consistency with other claim language.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/564,268 in view of Haraszti (NPL Document Title – Exosomes Produced from 3D Cultures of MSCs by Tangential Flow Filtration Show Higher Yield and Improved Activity, see in IDS filed 05/14/2025). This is a provisional nonstatutory double patenting rejection.
Regarding claim 1, the copending recites an isolation and purification method of extracellular vesicles (see copending claim 1; an exosome, see copending claim 5 and an exosome is a type of extracellular vesicle; while the copending claims do not explicitly a plurality of extracellular vesicles but this is obvious in light of copending claims), the isolation and purification method comprising filtering…containing extracellular vesicles through a hollow fiber membrane (see copending claim 1),
wherein
the hollow fiber membrane has an inner diameter of 0.2 mm to 1.4 mm and a molecular weight cut-off of 100000 to 1000000 (see copending claim 1),
the filtering includes
a first filtration process of press-fitting the culture supernatant of the mesenchymal stem cells from a first opening on one end side of the hollow fiber membrane and filtering the culture supernatant to separate the culture supernatant into a permeate and a first concentrate (see copending claim 1), and
a second filtration process of press-fitting the first concentrate from a second opening on the other end side of the hollow fiber membrane and filtering the first concentrate to separate the first concentrate into a permeate and a second concentrate (see copending claim 1),
a concentrate is produced in which a concentration of the extracellular vesicles is increased by alternating tangential flow filtration in which the first filtration process and the second filtration process are alternately performed a plurality of times (see copending claim 1), and
a membrane surface velocity in the first filtration process and the second filtration process is 0.3 m/sec to 2 m/sec (see copending claim 1).
The copending claims do not recite filtering a culture supernatant of mesenchymal stem cells.
In a related field of endeavor, Haraszti teaches an exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity (see ABS) comprising the steps filtering a culture supernatant of mesenchymal stem cells (see “3D Culture and Tangential Flow Filtration Enhances Exosome Yield” on pg. 2839).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the method of the copending claims by incorporating the step of filtering a culture supernatant of mesenchymal stem cells as disclosed by Haraszti because mesenchymal stem cells are considered to be an attractive cell type for therapeutic exosome production (Haraszti, see ABS on pg. 2838).
Regarding claim 2, the copending claims and the Haraszti teach the isolation and purification method of extracellular vesicles according to claim 1, wherein in the filtering, the culture supernatant of the mesenchymal stem cells is filtered with a microfiltration membrane having a pore size of 0.1 um to 0.5 um, and then the first filtration process and the second filtration process are alternately performed a plurality of times using a filtrate of the micro filtration membrane (see copending claim 2).
Regarding claim 3, the copending claims and the Haraszti teach the isolation and purification method of extracellular vesicles according to claim 1, wherein the first filtration process is performed in a manner that the culture supernatant of the mesenchymal stem cells or the second concentrate produced in the second filtration process is diluted by adding a buffer solution, and then the first filtration process is performed (see copending claim 3).
Regarding claim 4, the copending claims and the Haraszti teach the isolation and purification method of extracellular vesicles according to claim 1, wherein in the first filtration process and the second filtration process, press-fitting is performed by introducing a gas selected from the group consisting of nitrogen gas, inert gas, carbon dioxide, and air filtered by a HEPA filter (see copending claim 4).
Regarding claim 5, the copending claims and the Haraszti teach the isolation and purification method of extracellular vesicles according to claim 1, wherein the method reduces, to 1/5 or less, an amount of protein contained in the culture supernatant of the mesenchymal stem cells containing the extracellular vesicles serving as a starting material (while not explicitly recited, this limitation is obvious in light of the copending pending).
Regarding claim 6, the copending claims and the Haraszti teach the isolation and purification method of extracellular vesicles according to claim 1, wherein a concentration of insulin in the concentrate isolated and purified is 5 mg/L or less (because of insulin is inherently present in extracellular vesicles or exosomes and therefore likely an overlapping range is present).
The examiner takes note of the fact that the prior art range overlaps the claimed range. Absent any additional and more specific information in the prior art, a prima facie case of obviousness exists. In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379 (Fed. Cir. 2003). MPEP 2144.05.
Regarding claim 7, the copending claims and the Haraszti teach the isolation and purification method of extracellular vesicles according to claim 1, wherein, based on an amount of the extracellular vesicles contained in the culture supernatant of the mesenchymal stem cells, an amount of extracellular vesicles contained in the concentrate, which is measured using an ExoScreen method, has a concentration ratio of 5 times or more and a recovery rate of 50% or more (while not explicitly recited, this limitation is obvious in light of the copending pending).
Regarding claim 8, the copending claims and the Haraszti teach the isolation and purification method of extracellular vesicles according to claim 1, wherein the hollow fiber membrane is a hollow fiber membrane module in which a plurality of hollow fiber membranes is accommodated in a case housing having a plurality of liquid inlet/outlet ports (see copending claim 6).
Regarding claim 9, the copending claims and the Haraszti teach the isolation and purification method of extracellular vesicles according to claim 1, wherein when the first filtration process and the second filtration process are alternately performed, a dilution factor of an object to be filtered in the first filtration process is increased as the number of times of performing the first filtration process and the second filtration process increases (see copending claim 7).
Regarding claim 10, the copending claims and the Haraszti teach the isolation and purification method of extracellular vesicles according to claim 1, wherein when the first filtration process and the second filtration process are alternately performed, a dilution factor of an object to be filtered in the first filtration process is increased in a range of 2 times in volume to 15 times in volume as the number of times of performing the first filtration process and the second filtration process increases (see copending claim 8).
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 18/727,760. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-19 of the reference application '760 fall within the scope of claims 1-10 of the instant invention, and therefore claims 1-10 of the instant invention are anticipated by claims 1-19 of the reference application '760. This is a provisional nonstatutory double patenting rejection.
Regarding claim 1, the copending claims recite an isolation and purification method of extracellular vesicles (see copending claim 1), the isolation and purification method comprising filtering a culture supernatant of mesenchymal stem cells containing extracellular vesicles through a hollow fiber membrane (see copending claims 3 and 9),
wherein
the hollow fiber membrane has an inner diameter of 0.2 mm to 1.4 mm and a molecular weight cut-off of 100000 to 1000000 (see copending claims 10-11),
the filtering includes
a first filtration process of press-fitting the culture supernatant of the mesenchymal stem cells from a first opening on one end side of the hollow fiber membrane and filtering the culture supernatant to separate the culture supernatant into a permeate and a first concentrate (see copending claim 11), and
a second filtration process of press-fitting the first concentrate from a second opening on the other end side of the hollow fiber membrane and filtering the first concentrate to separate the first concentrate into a permeate and a second concentrate (see copending claim 11),
a concentrate is produced in which a concentration of the extracellular vesicles is increased by alternating tangential flow filtration in which the first filtration process and the second filtration process are alternately performed a plurality of times (see copending claim 11), and
a membrane surface velocity in the first filtration process and the second filtration process is 0.3 m/sec to 2 m/sec (see copending claim 11).
Regarding claim 2, the copending claims recite the isolation and purification method of extracellular vesicles according to claim 1, wherein in the filtering, the culture supernatant of the mesenchymal stem cells is filtered with a microfiltration membrane having a pore size of 0.1 um to 0.5 um, and then the first filtration process and the second filtration process are alternately performed a plurality of times using a filtrate of the micro filtration membrane (see copending claim 12).
Regarding claim 3, the copending claims recite the isolation and purification method of extracellular vesicles according to claim 1, wherein the first filtration process is performed in a manner that the culture supernatant of the mesenchymal stem cells or the second concentrate produced in the second filtration process is diluted by adding a buffer solution, and then the first filtration process is performed (see copending claim 13).
Regarding claim 4, the copending claims recite the isolation and purification method of extracellular vesicles according to claim 1, wherein in the first filtration process and the second filtration process, press-fitting is performed by introducing a gas selected from the group consisting of nitrogen gas, inert gas, carbon dioxide, and air filtered by a HEPA filter (see copending claim 14).
Regarding claim 5, the copending claims recite the isolation and purification method of extracellular vesicles according to claim 1, wherein the method reduces, to 1/5 or less, an amount of protein contained in the culture supernatant of the mesenchymal stem cells containing the extracellular vesicles serving as a starting material.
Regarding claim 6, the copending claims recite the isolation and purification method of extracellular vesicles according to claim 1, wherein a concentration of insulin in the concentrate isolated and purified is 5 mg/L or less.
Regarding claim 7, the copending claims recite the isolation and purification method of extracellular vesicles according to claim 1, wherein, based on an amount of the extracellular vesicles contained in the culture supernatant of the mesenchymal stem cells, an amount of extracellular vesicles contained in the concentrate, which is measured using an ExoScreen method, has a concentration ratio of 5 times or more and a recovery rate of 50% or more (see copending claim 16).
Regarding claim 8, the copending claims recite the isolation and purification method of extracellular vesicles according to claim 1, wherein the hollow fiber membrane is a hollow fiber membrane module in which a plurality of hollow fiber membranes is accommodated in a case housing having a plurality of liquid inlet/outlet ports (see copending claim 17).
Regarding claim 9, the copending claims recite the isolation and purification method of extracellular vesicles according to claim 1, wherein when the first filtration process and the second filtration process are alternately performed, a dilution factor of an object to be filtered in the first filtration process is increased as the number of times of performing the first filtration process and the second filtration process increases (see copending claim 18).
Regarding claim 10, the copending claims recite the isolation and purification method of extracellular vesicles according to claim 1, wherein when the first filtration process and the second filtration process are alternately performed, a dilution factor of an object to be filtered in the first filtration process is increased in a range of 2 times in volume to 15 times in volume as the number of times of performing the first filtration process and the second filtration process increases (see copending claim 19).
Pertinent Art
Wales (US 2019/0241856) teaches a reversible liquid filtration system (see ABS and Figs. 4a-4d and 5a-5b).
Lee (US 2022/0387936) teaches a filter structure having function of selectively collecting water through opposite ends thereof and filtering method using same (see ABS and Figs. 4-5).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EKANDRA S. MILLER-CRUZ whose telephone number is (571)270-7849. The examiner can normally be reached M-Th 7 am - 6 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Benjamin L. Lebron can be reached at (571) 272-0475. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EKANDRA S. MILLER-CRUZ/Primary Examiner, Art Unit 1773