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 .
Response to Arguments
Applicant's arguments filed 09/04/2026 regarding the 35 U.S.C. 112 (b) rejections, have been fully considered, and they are not persuasive because 112 issues concerning indefiniteness previously addressed remain in independent claim 1 and in other dependent claims and because new 112 (b) issues were necessitated by the amendment of 09/04/2026 concerning claims 8-13, now being dependent on claim 7, which has been canceled by the Amendment, thus claims 1-6 and 8-16 now remain rejected under 35 U.S.C. 112(b).
Applicant’s arguments, filed 09/04/2026, with respect to the rejection of claims 1-9, 12 and 14, under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Gho et al PGPUBS Document US 2020/0164284, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn.
However, upon further consideration, a new ground of rejection of claims 1-9, 12 and 14 under 35 U.S.C. 103 is made as being obvious over Gho et al PGPUBS Document US 2020/0164284 (Gho) in view of Hagihara et al PGPUBS Document US 2018/0016547 (Hagihara).
Applicant’s arguments, filed 09/04/2026, with respect to the rejection of claims 10, 11 and 14-16, under 35 U.S.C. 103 as being obvious over Gho et al PGPUBS Document US 2020/0164284 (Gho) in view of the Escapenet Machine Translation of Patent Publication CN 111295450 (hereinafter "450"), have been fully considered and are persuasive. Therefore, this rejection has also been withdrawn.
However, upon further consideration, a new ground of rejection of claims 10, 11 and 14-16 under 35 U.S.C. 103 is made as being obvious over Gho et al PGPUBS Document US 2020/0164284 (Gho) in view of the Escapenet Machine Translation of Patent Publication CN 111295450 (hereinafter "450") and Hagihara et al PGPUBS Document US 2018/0016547 (Hagihara).
Regarding both the 35 U.S.C. 102 and 103 rejections, Applicant’s specifically argue that Gho ‘484 lacks a teaching of the method being performed on a large scale, such that the method purifies greater than 30 ml of culture.
It is submitted that Gho ‘484 specifically discloses [0045 re “mass purification”, thus “large scale purification” of extracellular vesicles].
Hagihara teaches a method and continuous cell cultivation device (Abstract, [0028]), in which the cell culture medium is purified by treating it with a polyimide membrane film in which cell culture of a continuous culturing apparatus is continuously circulated from a 150 ml volume medium reservoir at a flow rate of 3 ml/min [0279 and 0280]. Hagihara teaches the method and device as being directed to meeting increasing demand for various medical purposes, met by mass production cell culturing using methodologies for efficient and convenient culturing of large volumes of cells [see 0003].
Thus, it would have been obvious to one of ordinary skill in the art of purifying bacterial cell cultures, to have performed the Gho ‘484, by designing the apparatus to enable continuous circulation of relatively large flow volumes of cell culture through a device or system for performing the purification steps, enabling purifying of volumes greater than 30 mL of culture, as cumulatively taught by Gho ‘484 and Hagihara, to enable meeting increasing demand for the purified vesicles, for one or more of various medical purposes, met by mass production cell culturing using methodologies for efficient and convenient culturing of large volumes of cells {Hagihara at [0003] and Gho ‘484 at [0045]}.
Double Patenting
Applicant’s acknowledgement of the Double Patenting Rejection of record of claims 1-7, (now of claims 1-6 in view of canceling of claim 7 in the 09/04/2026 Amendment) based on being unpatentable over claims 1 and 4-7 of Gho et al U.S. Patent No. 11,904,259 in view of Gho et al PGPUBS Document US 2021/0046172 and statement that applicant will take appropriate corrective action of filing a terminal disclaimer or distinguishing the claims once allowable subject matter is obtained in one of the applications is noted.
The claim amendments made in the Amendment of 09/04/2026 ha resulted in the Double Patenting rejection being modified to being over claims 1-6, based on being unpatentable over claims 1 and 4-7 of Gho et al U.S. Patent No. 11,904,259 in view of Gho et al PGPUBS Document US 2021/0046172 and Hagihara et al PGPUBS Document US 2018/0016547 (Hagihara).
This 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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4-7 of Gho et al U.S. Patent No. 11,904,259 (Gho ‘259) in view of Gho et al PGPUBS Document US 2021/0046172 (Gho ‘172) and Hagihara et al PGPUBS Document US 2018/0016547 (Hagihara). The instant claim limitations are encompassed in the claim limitations recited in patent ‘172 in the following side-by-side comparison, with the exception of the recitation of “isolation of extracellular vesicles”, recited in claim 1 of Gho ‘259 versus recitation of “large-scale purification, of specifically, bacterial, extracellular vesicles in the instant claims, and of recitation of “wherein the method purifies greater than 30 mL of culture” in instant claim 1, as currently amended.
The side-by-side comparison of the instant claims versus what is claimed in Gho ‘259 is as follows:
1 . A method for purification of extracellular vesicles (Gho ‘ 259, claim 1 preamble “isolating extracellular vesicles”), comprising the steps of:
(a) adding calcium cations or cobalt cations to a cell culture (Gho ‘259, claim 1, part (a));
(b) reacting the extracellular vesicles contained in the cell culture with the calcium cations or cobalt cations to form insoluble complex (Gho ‘259, claim 1, part (b));
(c) isolating the complex of the extracellular vesicles and the calcium cations or cobalt cations from the cell culture; and
(d) isolating the calcium cations or cobalt cations from the complex to purify the extracellular vesicles (Gho ‘259, claim 1, part (d)).
2. The method of claim 1, wherein the concentration of the calcium cations or cobalt cations is 1 to 1,000 mM, 1 to 500 mM, 1 to 100 mM, 5 to 100 mM, 5 to 50 mM, 5 to 20 mM, 5 to 15 mM, or 5 to 10 mM (Gho ‘259, claim 1, part (a) regarding “calcium ions being added at a concentration of 10mM or greater”, encompassing a plurality of the instantly recited ranges).
3. The method of claim 2, wherein the concentration of calcium cations or cobalt cations is 5 to 20 mM (Gho ‘259, claim 1, part (a) regarding “calcium ions being added at a concentration of 10mM or greater”, encompassing the instantly recited range of 5 to 20 mM).
4. The method of claim 1, wherein step (c) is conducted by one or more methods selected from the group consisting of centrifugation, ultracentrifugation, filtration, ultrafiltration, gravity, dialysis, sonication, density gradient, and size exclusion (Gho ‘259, claim 1, part c).
5. The method of claim 1, wherein step (d) is conducted by one or more methods selected from the group consisting of adding a chelate agent, changing a pH value, or changing the concentration of imidazole, histidine, ethylenediamine tetraacetate (EDTA) or a salt (Gho ‘259, claim 4).
6. The method of claim 5, wherein the chelate agent is one or more selected from the group consisting of iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), tris-(carboxymethyl)ethylenediamine (TED), ethylenediamine, ethylenediamine tetraacetate (EDTA), alkylenediamine triacetic acid, diethylenetriaminepentaacetic acid (DTPA), ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), phosphoserine, and 1,4,7-triazocyclononane (TACN), (Gho ‘259, claim 5).
The instant claim limitations are encompassed in the claim limitations recited in patent ‘172 as above, with an exception of the recitation of “isolation of extracellular vesicles” recited in claim 1 of Gho ‘259 versus recitation of “large-scale purification, and of specifically, bacterial, extracellular vesicles in the instant claims.
However, Gho ‘172 teaches to use bacterial extracellular vesicles that have been cultured and isolated, i.e. “purified”, from a bacterial cell culture medium, with the benefit of reducing the toxicity of the vesicles, so as to be delivered as a vaccine pharmaceutical composition of reduced toxicity [0002, 0007 and 0045], the “isolation” concerning purification steps selected from ultracentrifugation, density gradient, filtration, dialysis, precipitation, chromatography and free flow electrophoresis.
Thus , it would have been obvious to one of ordinary skill in the biochemistry arts to have applied the isolation of extracellular vesicle method steps recited in the claims of ‘172 to bacterial extracellular vesicles that have been cultured and isolated, i.e. “purified”, from a bacterial cell culture medium including purification steps, as taught by ‘Gho ‘172, in order to reduce the toxicity of the vesicles so as to be delivered as a vaccine pharmaceutical composition of reduced toxicity.
In addition, Gho ‘172 teaches the resulting extracellular vesicles being of relatively large size of 40-50 nm diameter [0155], and produced as a great number of extracellular vesicles [0156] hence the method being “large scale”.
Hence, it would have been also obvious to one of ordinary skill in the biochemistry arts to have applied the isolation of extracellular vesicle method steps recited in the claims of ‘172 to produce bacterial extracellular vesicles, on a large scale, as taught by ‘Gho ‘172, in order to produce more pharmaceutical product of benefit to patients.
Claim 1 now also differs from what is claimed in Gho ‘259 by requiring “wherein the method purifies greater than 30 mL of culture”.
Hagihara teaches a method and continuous cell cultivation device (Abstract, [0028]), in which the cell culture medium is purified by treating it with a polyimide membrane film in which cell culture of a continuous culturing apparatus is continuously circulated from a 150 ml volume medium reservoir at a flow rate of 3 ml/min [0279 and 0280]. Hagihara teaches the method and device as being directed to meeting increasing demand for various medical purposes, met by mass production cell culturing using methodologies for efficient and convenient culturing of large volumes of cells [see 0003].
It would have been obvious to one of ordinary skill in the art to have modified the method of the claims of Gho ‘259, by modifying the claimed method to include enabling of continuous circulation of relatively large flow volumes of cell culture through a device or system for performing the purification steps, enabling purifying of volumes greater than 30 mL of culture, as taught by Hagihara, to enable meeting increasing demand for the purified vesicles, for one or more of various medical purposes, met by mass production cell culturing using methodologies for efficient and convenient culturing of large volumes of cells {Hagihara at [0003] }.
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.
Claims 1-16 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
In claim 1, in the preamble, “large-scale” is deemed to be a relative term of unclear scope or bounds, since there is no clear and distinct criteria for determining what amount or volume of “purification of bacterial extracellular vesicles” constitutes a large-scale amount or volume, versus “a medium scale or small scale” amount or volume, regarding recitation of “wherein the method purifies greater than 30 mL of culture”, it is unclear whether such amount is an amount of purification which occurs over a given time period of continuous purification, or is a total amount or amount of a batch of cell culture.
Claims 8 and 12 are indefinite and undefined, since they depend from claim 7, which is now canceled, and thus not present, with claims 9-11 and 13 dependent from claims 8 and 12, respectively, are similarly now also being indefinite and undefined.
Additionally, recitations in each of claims 8-11 of “the pretreatment step” and in each of claims 12 and 13 of “the post-treatment step” now lack antecedent basis, due to such canceling of claim 7 from which they formerly depended.
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 non-obviousness.
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 1-6, 8, 9, 12 and 13 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Gho et al PGPUBS Document US 2020/0164284 published more than one year before the effective filing date of the instant application (Gho ‘484) in view of Hagihara et al PGPUBS Document US 2018/0016547 (Hagihara).
Referenced paragraph numbers of the applied PGPUBS Documents are identified with “[ ]” symbols.
For independent claim 1, Gho ‘484 discloses: a method for large-scale purification of bacterial extracellular vesicles ([0018 and 0019 regarding isolation of extracellular vesicles from “biosamples” which may be selected from “bacterial cell culture medium”] and [0045 re “mass purification”, thus “large scale purification” of extracellular vesicles]), thus , comprising the steps of:
(a) adding calcium cations or cobalt cations to a bacterial cell culture [0016, part (a) concerning adding cations], and [0023-0024 regarding cations added to form a complex being selected from calcium and cobalt ions];
(b) reacting bacterial extracellular vesicles contained in the bacterial cell culture with the calcium cations or cobalt cations to form insoluble complex [also see 0016, part (b) concerning reacting cations with extracellular vesicles to form a complex];
(c) isolating the complex of the bacterial extracellular vesicles and the calcium cations or cobalt cations from the bacterial cell culture ([0016, part c), [0018] and [0019] concerning separating the vesicle-cation complex from the sample containing the extracellular vesicles) ; and
(d) isolating the calcium cations or cobalt cations from the complex to purify the bacterial extracellular vesicles [0016, part (d) concerning separating the cations from the complex to purify extracellular vesicles].
Claim 1, and hence all claims dependent therefrom now also differ from Gho ’484 by requiring “wherein the method purifies greater than 30 mL of culture.
Gho ‘484 specifically discloses [0045 re “mass purification”, thus “large scale purification” of extracellular vesicles].
Hagihara teaches a method and continuous cell cultivation device (Abstract, [0028]), in which the cell culture medium is purified by treating it with a polyimide membrane film in which cell culture of a continuous culturing apparatus is continuously circulated from a 150 ml volume medium reservoir at a flow rate of 3 ml/min [0279 and 0280]. Hagihara teaches the method and device as being directed to meeting increasing demand for various medical purposes, met by mass production cell culturing using methodologies for efficient and convenient culturing of large volumes of cells [see 0003].
It would have been obvious to one of ordinary skill in the art of purifying bacterial cell cultures, to have performed the Gho ‘484,
by designing the apparatus to enable continuous circulation of relatively large flow volumes of cell culture through a device or system for performing the purification steps, enabling purifying of volumes greater than 30 mL of culture,
as cumulatively taught by Gho ‘484 and Hagihara,
to enable meeting increasing demand for the purified vesicles, for one or more of various medical purposes, met by mass production cell culturing using methodologies for efficient and convenient culturing of large volumes of cells {Hagihara at [0003] and Gho ‘484 at [0045]}.
For dependent claims, Gho ‘484 further discloses:
for claim 2, wherein the concentration of the calcium cations or cobalt cations is 1 to 1,000 mM [0097 regarding copper cations being added to cell cultures to reach a final concentration of 20 mM, to thereby harvest extracellular vesicles], thus being encompassed within one or more of the alternative claimed ranges;
for claim 3, wherein the concentration of calcium cations or cobalt cations in the bacterial culture is 5 to 20 mM (again see [0097 regarding copper cations being added to cell cultures to reach a final concentration of 20 mM, to thereby harvest extracellular vesicles] thus being encompassed within the claimed ranges]);
for claim 4, wherein step (c) is conducted by one or more methods selected from the group consisting of centrifugation, ultracentrifugation, filtration, ultrafiltration, dialysis, sonication, density gradient, and size exclusion [0026 regarding a plurality of such method steps];
for claim 5, wherein step (d) is conducted by one or more methods selected from the group consisting of adding a chelate agent, changing a pH value, or changing the concentration of imidazole, histidine, ethylenediamine tetraacetate (EDTA) or a salt ([0027-0030 re step d) including addition of various of these chelating agents, [0031 re changing of pH value] and [0030 regarding adding of, thus changing concentration of imidazole, histidine, ethylenediamine tetraacetate (EDTA)]);
for claim 6, wherein the chelate agent is one or more selected from the group consisting of iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), tris-(carboxymethyl)ethylenediamine (TED), ethylenediamine, ethylenediamine tetraacetate (EDTA), alkylenediamine triacetic acid, diethylenetriaminepentaacetic acid (DTPA), ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), phosphoserine, and 1,4,7-triazocyclononane (TACN) [0030 listing a plurality of these chelating agents];
for claim 7, wherein the method further comprises
a pre-treatment step of the bacterial cell culture prior to step (a) [0034 re pretreating the sample before cations are added to a sample],
further comprises a post-treatment step of the purified bacterial cell culture after step (d) [0036 re post-treating the separated extracellular vesicles], or
comprises both of the pre-treatment and post-treatment steps ([0034 re pre-treating, and 0036 re post-treating];
for claim 8, wherein the or a pre-treatment step is conducted by one or more methods selected from the group consisting of centrifugation, filtration, ultrafiltration, size exclusion, desalting column chromatography, size exclusion chromatography, ion exchange chromatography, affinity chromatography, polymer precipitation, salt precipitation, organic solvent precipitation, aqueous two-phase separation, and enzyme treatment [0035 re a plurality of the above pre-treatment steps to partially purify];
for claim 9, wherein the or a pre-treatment step is conducted by centrifugation, filtration, polymer precipitation or salt precipitation (again these 4 specific steps recited in [0035]);
for claim 12, wherein the or a post-treatment step is conducted by one or more methods selected from the group consisting of centrifugation, filtration, ultrafiltration, dialysis, sonication, density gradient, size exclusion, desalting column chromatography, size exclusion chromatography, ion exchange chromatography, affinity chromatography, polymer precipitation, salt precipitation, organic solvent precipitation, aqueous two-phase separation and enzyme treatment [0037 regarding conducting a plurality of such method steps]; and,
for claim 13, wherein the or a post-treatment step is conducted by ultrafiltration, dialysis, size exclusion, size exclusion chromatography, ion exchange chromatography, polymer precipitation or salt precipitation (again see [0037 regarding conducting a plurality of such method steps]).
Claims 10, 11 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Gho et al PGPUBS Document US 2020/0164284 published more than one year before the effective filing date of the instant application (Gho ‘484), as applied to claims 1-9, 12 and 13, in view of the Escapenet Machine Translation of Patent Publication CN 111295450. Referenced paragraph numbers of the applied PGPUBS Documents and the applied Escapenet Machine Translation publication are identified with “[ ]” symbols.
For claim 10, Gho ‘484 further discloses wherein the or a pre-treatment step is conducted by filtration or ultrafiltration [0035]. Claim 10 differs from ‘484 by requiring that the filtration comprises tangential flow filtration (TFF).
Publication (‘450) teaches cost-effective, efficient and scalable methods of removing impurities from cultured bacterial polysaccharides used to produce capsuled vaccine product [0005-0007]. Since Publication ’450 concerns preparation of a medical or pharmaceutical capsuled product obtained from culturing bacteria it is deemed to be analogous prior art with respect to Gho ‘484, since it is also directed to a medical or pharmaceutical capsuled product obtained from culturing bacteria.
Publication ‘450 teaches the purification comprising an ultrafiltration step comprising TFF, which results in a high yield of greater than 70% and removal of impurities to an extent in which the capsuled product contains less than or equal to 1% protein and less than or equal to 1% nucleic acid, relative to the total product [0026], with such purification method requiring a very short time through efficient, simple and commercially scalable steps to produce products which meet or exceed various world-wide health standards.
Publication ‘450 describes the disclosed extracellular vesicles as being obtained from culture medium containing various membrane components, proteins and RNA and DNA nucleic acid material in [0006], hence suggests a need to remove undesirable or excess proteins and nucleic acids.
It would have been obvious to one of ordinary skill in the purifying biochemical medical products to have practiced the method of Gho ‘484, by conducting the disclosed ultrafiltration step utilizing a tangential flow filtration (TFF) mechanism, as taught or suggested by ‘450, to result in production of more highly purified extracellular vesicles, in which protein and nucleic acid fragment impurities have been substantially removed, in a process step requiring very short process time through efficient, simple and commercially scalable steps to produce products which meet or exceed various world-wide health standards.
For claim 11, dependent on claim 10, Gho ‘484 further discloses wherein the pre-treatment step is further conducted by polymer precipitation or salt precipitation after the filtration (TFF), (see [0035 regarding the pretreating optionally adopting ultrafiltration in combination with polymer precipitation]).
Claim 14 differs from the method of Gho ‘484 by requiring wherein the method further comprises an enzyme treatment step for removing nucleic acid particles derived from bacteria prior to step (a), after step (b), after step (c), or after step (d).
Publication (‘450) teaches cost-effective, efficient and scalable methods of removing impurities from cultured bacterial polysaccharides used to produce capsuled vaccine product [0005-0007]. Since Publication ’450 concerns preparation of a medical or pharmaceutical capsuled product obtained from culturing bacteria it is deemed to be analogous prior art with respect to Gho ‘484, since it is also directed to a medical or pharmaceutical capsuled product obtained from culturing bacteria.
Gho ‘484 further discloses wherein the pre-treatment step is conducted by filtration or ultrafiltration [0035].
Publication ‘450 also teaches purification of the medical product comprising removal of residual DNA and RNA, i.e. “nucleic acid particles” from the culture medium by a combination of method steps comprising ultrafiltration and enzymatic treatment with a enzymatic lyase, or specifically Benzonase, to remove such impurities [0029-0032].
It would have been obvious to one of ordinary skill in the purifying biochemical medical products to have practiced the method of Gho ‘484, by combining the disclosed ultrafiltration step with an enzyme treatment step, as taught or suggested by ‘450, to result in production of more highly purified extracellular vesicles, in which protein and nucleic acid fragment impurities have been substantially removed
For claim 15, publication ‘450 specifically teaches wherein the enzyme treatment step is conducted by using benzonase, teaching that such enzyme removes residual geonome DNA and RNA from a cellular mixture by a hydrolyzing mechanism.
Thus, it would have been additionally obvious to have selected benzonase as the enzyme which is employed in the Gho ‘484 method, as modified in view of publication ‘450, so as to effectively remove residual geonome DNA and RNA from the cellular mixture by a hydrolyzing mechanism.
For claim 16, Gho ‘484 in view of publication ‘450, further suggests wherein the method comprises the step of performing ion exchange chromatography in combination with or after the treatment with benzonase [0035 regarding the pretreatment step as employing a combination of ultrafiltration and ion exchange chromatography.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Primary Examiner Joseph Drodge at his direct government formal facsimile phone number telephone number of 571-272-1140. The examiner can normally be reached on Monday-Friday from approximately 8:00 AM to 1:00PM and 2:30 PM to 5:30 PM.
If attempts to reach the examiner are unsuccessful, the examiner' s supervisor, Benjamin Lebron, of Technology Center Unit 1773, can reached at 571-272-0475.
The telephone number, for official, formal communications, for the examining group where this application is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from the Patent Examiner. Unpublished application information in Patent Center is available to registered users. Visit https:///www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https:///www.uspto.gov/patents/apply/patents/docx for information about filing in DOCX format. For additional questions contact the Electronic Business Center EBC) at 866-217-9197 (toll free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (in USA or Canada) or 571-272-1000.
JWD
10/01/2026
/JOSEPH W DRODGE/ Primary Examiner, Art Unit 1773
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