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 .
Status of Claims
The amendments and arguments filed 1 August 2025 are acknowledged and have been fully considered. Claims 1-20 are currently pending. Claims 1-7 and 9-10 are amended; no claims are cancelled; claims 11-16 are withdrawn; claims 17-20 are new.
Claims 1-10 and 17-20 are examined on the merits herein.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. In particular, the rejection of claims 1-7 and 9-10 under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendments to the claims. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
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.
Claim 19 is NEWLY 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 19 recites the limitation " the dual asymmetric centrifuge" in line 1. There is insufficient antecedent basis for this limitation in the claim. For examination purposes, claim 19 is interpreted as being dependent on claim 18.
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.
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 and 4-10 are MAINTAINED rejected under 35 U.S.C. 103 as being unpatentable over Massing (US 2008/0193511; of record) in view of Sui et al. (Polymer Chemistry, 2015, Vol. 6, 691-696; of record).
Claim 17 is NEWLY rejected under 35 U.S.C. 103 as being unpatentable over Massing (US 2008/0193511; of record) in view of Sui et al. (Polymer Chemistry, 2015, Vol. 6, 691-696; of record).
Claim 1 is drawn to a method for producing polymersomes, comprising the steps of
preparing a mixture comprising an aqueous solvent, a copolymer and a dispersing aid
hydrating the copolymer in the mixture, and
processing the mixture in a dual centrifuge (more specifically a dual asymmetric centrifuge (Claim 17)) to obtain polymersomes.
Claim 4 is drawn to the method of claim 1, wherein the copolymer employed in the step of preparing a mixture is in a dehydrated state.
Claim 6 is drawn to the method of claim 1, wherein the mixture comprises 0.5 to 40 wt% copolymer, 4.5 to 60 wt% aqueous solution and 20 to 95 wt% dispersing aid.
Claim 7 is drawn to the method of claim 1, wherein the dispersing aid is highly spherical beads made of glass and wherein the dispersing aid has a diameter distribution with average diameters of 0.1 to 2mm.
Claim 8 is drawn to the method of claim 1, wherein the mixture is free from organic solvents.
Claim 9 is drawn to the method of claim 1, wherein the copolymer is a block copolymer (more specifically PEG-b-PCL (Applicant’s elected species)).
Claim 10 is drawn to the method of claim 1, wherein the mixture additionally comprises a pharmaceutically active ingredient suitable to be enclosed in the polymersomes.
Massing teaches a method for producing lipid-based nanoparticles using a dual asymmetrical centrifuge (Abstract), further teaching the lipid-based nanoparticles being liposomes (Pars. [0001] and [0229]). Massing further teaches in Par. [0234] the method comprising combining lipids and the sPLA2 inhibitor 2-(R)-1-O-phosphocholine-2-N-laurinoyloctadecane (i.e., a pharmaceutically active ingredient) and dissolving in CHCl3 and methanol; removing the solvent to obtain a dry lipid film; combining 100 mg of the lipid mixture, 200 mg of sterile glass beads having a diameter of 1mm, and 150 µL of PBS buffer (i.e., hydrating the lipid); and speed mixing for 15 minutes to obtain vesicles. Massing further teaches “Within the context of the present invention, “speed mixing” means the use of a Speedmixer® or another DAC, preferably a type DAC 150 FVZ Speedmixer® of the company Hauschild GmbH und Co KG having a counter-rotation ratio of approximately 2.8:1 or 4.2:1, especially preferred 4.2:1, or a dual asymmetric centrifuge having a similar counter-rotation ratio” (Par. [0078]).
The amounts of lipid, glass beads, and PBS buffer in the method of Massing correspond to 22.2 wt% lipid, 33.3 wt% aqueous solution, and 44.5 wt% dispersing aid as calculated by examiner, overlapping with the instantly claimed ranges.
As such, Massing teaches a method for producing liposomes comprising the steps of preparing a mixture comprising an aqueous solvent, a lipid, and a dispersing aid, rehydrating the lipid, and processing the mixture in a dual asymmetric centrifuge to obtain liposomes, wherein the lipid employed in the step of preparing a mixture is in a dehydrated state, wherein the dispersing aid is spherical beads made of glass and having a diameter of 0.1 to 2mm, wherein the mixture is free from organic solvents, and wherein the mixture additionally comprises a pharmaceutically active ingredient.
The method of Massing differs from the instantly claimed method in the following ways:
the mixture of Massing does not comprise a block copolymer.
Yet, as to 1: Massing further teaches the use of membrane-forming amphiphiles such as block polymers as the membrane-forming lipid (par. [0100]).
Sui et al. teach a method for forming biodegradable polymersomes comprising PEG-b-PCL (Abstract). Sui et al. further teach that PEG-b-PCL is one of the most studied candidates for production of biodegradable polymersomes for biomedical applications as PCL is a biodegradable polymer that is FDA-approved for use in drug delivery, and PEG is nontoxic and can help prolong the blood circulation time of polymersomes (Pg. 691 right column first paragraph). Sui et al. further teach the polymersomes being formed by a similar centrifugation method (Pg. 694 left column last paragraph – right column first paragraph).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Massing to include PEG-b-PCL as taught by Sui et al. It would have been obvious to combine the known method of nanoparticle production with the known use of PEG-b-PCL for biodegradable polymersomes to yield the predictable result of a method to produce biodegradable polymersomes, with a reasonable expectation of success.
Based on all of the foregoing, claims 1, 4, and 6-10 are rejected as prima facie obvious.
Claim 5 is drawn to the method of claim 1, wherein the speed of the dual asymmetric centrifuge in the processing step is 2000 to 5000 rpm, and wherein the step of processing is carried out for a time between 10 and 50 minutes.
Massing further teaches the processing step “ is performed with at least 200 rpm, preferably at least 1000 rpm and maximally 4000 rpm, especially preferred at from 2000 to 3540 rpm, most preferred at from 2500 to 3540 rpm” and “the centrifugation time is from 30 s to 1 h, preferably from 1 to 30 min, especially preferred from 3 to 20 min” (Par. [0030]), overlapping with the instantly claimed ranges.
As such, claim 5 is also rejected as prima facie obvious.
Claims 2-3 are MAINTAINED rejected under 35 U.S.C. 103 as being unpatentable over Massing and Sui et al. as applied to claims 1, 4-10, and 17 above, and further in view of Pohlit et al. (Biomacromolecules, 2015, Vol. 16, 3103-3111; of record).
Claim 20 is NEWLY rejected under 35 U.S.C. 103 as being unpatentable over Massing and Sui et al. as applied to claims 1, 4-10, and 17 above, and further in view of Pohlit et al. (Biomacromolecules, 2015, Vol. 16, 3103-3111; of record).
The teachings of Massing and Sui et al. have been set forth above.
Claim 2 is drawn to the method of claim 1, wherein a step of homogenizing the mixture is carried out before the step of processing the mixture.
Claim 3 is drawn to the method of claim 2, wherein the duration of homogenizing is at least 1 minute.
Claim 20 is drawn to the method of claim 4, wherein a step of hydrating is carried out for at least 10 minutes.
Massing and Sui et al. do not teach a step of homogenizing the mixture prior to processing.
However, Pohlit et al. teach a similar double asymmetric centrifugation method of producing liposomes (Abstract). Pohlit et al. further teach the method comprising preparing a mixture of the lipids, a block copolymer, an active ingredient, and an aqueous solvent; homogenizing the mixture for 2 minutes in a standard centrifuge to guarantee contact between the dried lipids and the liquid phase; incubating the homogenized mixture for 10 minutes (i.e., hydrating for at least 10 minutes); and processing in the dual asymmetric centrifuge (Pg. 3105 left column fourth paragraph).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Massing and Sui et al. to include a step of homogenizing the mixture prior to processing as taught by Pohlit et al. It would have been obvious to apply the known homogenizing technique to improve the similar method of preparing polymersomes in the same way, by guaranteeing contact between the dried block polymer and aqueous phase to ensure hydration of the polymer, with a reasonable expectation of success.
As such, claims 2-3 and 20 are rejected as prima facie obvious.
Claims 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Massing et al., Sui et al., and Pohlit et al. as applied to claims 2-3 and 20 above, and further in view of Cicko et al. (Journal of Controlled Release, 2008, Vol. 125, 16-24 cited on Applicant’s IDS filed 2 September 2022).
The teachings of Massing et al., Sui et al., and Pohlit et al. have been set forth above.
Claim 18 is drawn to the method of claim 2, wherein the step of homogenizing the mixture is carried out in a dual asymmetric centrifuge.
Pohlit et al. teaches the homogenization step occurring in a standard centrifuge (Pg. 3105 left column fourth paragraph).
Massing et al., Sui et al., and Pohlit et al. do not teach the step of homogenizing the mixture being carried out in a dual asymmetric centrifuge.
However, Cicko et al. teach the formation of liposomes via dual asymmetric centrifugation (Title). Cicko et al. further teach “While the conventional centrifugation constantly pushes the sample material outwards, this additional rotation constantly forces the sample material towards the center of the centrifuge. This unique combination of two contra rotating movements results in shear forces and thus, in efficient homogenization” (Abstract).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Massing et al., Sui et al., and Pohlit et al. to utilize a dual asymmetric centrifuge in the homogenization step. It would have been obvious to substitute one form of centrifuge suitable for homogenization for another to obtain the predictable result of a method with more efficient homogenization, with a reasonable expectation of success.
As such, claim 18 is rejected as prima facie obvious.
Claim 19 is drawn to the method of claim 18, wherein the speed of the dual asymmetric centrifuge in the step of homogenizing the mixture is 2000 to 5000 rpm.
Cicko et al. further teach the use of speeds between 1000 to 4000 rpm for homogenization (Pg. 22 right column second paragraph), overlapping with the instantly claimed range.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Massing et al., Sui et al., Pohlit et al., and Cicko et al. to utilize a speed of between 2000 and 5000 rpm in homogenization. It would have been obvious to combine the known method of forming polymersomes with the known DAC speeds suitable for homogenization to yield the predictable result of a method for forming polymersomes, with a reasonable expectation of success.
As such, claim 19 is rejected as prima facie obvious.
Response to Arguments
Applicant's arguments filed 1 August 2025 have been fully considered but they are not persuasive.
Applicant argues on pg. 7 of the remarks that Massing et al. does not teach or suggest the production of either liposomes or polymersomes, and modifying the method of Massing et al. with the teachings of Sui et al. would render Massing et al. unsuitable for its intended purpose.
This argument is not persuasive. Massing et al. explicitly teach the formation of liposomes (see e.g., claim 1, par. [0229]), and further teach substitution of block polymers for the lipid (Par. [0100]), indicating that the method is suitable for the formation of polymersomes. As such, modifying the method of Massing et al. with the teachings of Sui et al. further yields a method suitable for the intended purpose of Massing et al.
Applicant further argues on pg. 7 of the remarks that Sui et al. is non-analogous art.
This argument is not persuasive. As discussed in MPEP 2141.01(a), it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. In the instant case, as Sui et al. teaches the formation of polymersomes, it is in the field of the inventor’s endeavor and is considered analogous art.
Applicant argues on pgs. 7-8 of the remarks that the methods of Massing et al. and Sui et al. are largely incompatible, and that incorporation of heating and stirring as taught by Sui et al. would be incompatible with the dual asymmetric centrifugation method of Massing et al.
This argument is not persuasive. The teachings of Sui et al. are relied upon to cure the deficiency of Massing et al. to the degree that Massing et al. do not teach the block polymer PEG-b-PCL. However, as Massing et al. teach the method as being suitable to form polymersomes by substituting block polymers for the lipids (Par. [0100]), and Sui et al. teach that PEG-b-PCL is suitable for forming polymersomes (Abstract), one of ordinary skill in the art would reasonably expect substitution of PEG-b-PCL in the method of Massing et al. to yield a method for forming polymersomes.
Applicant argues on pg. 8 of the Remarks that Sui et al. alone would not anticipate or render obvious the subject matter of the instant claims.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues on pg. 8 of the remarks that Massing et al. is non-analogous art as it does not teach the preparation of polymersomes.
This argument is not persuasive. As discussed in MPEP 2141.01(a), it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. In the instant case, Massing et al. teach the use of a dual asymmetric centrifuge to form particles such as liposomes. As such, Massing et al. is considered to be reasonably pertinent to the particular problem with which the inventor was concerned and as such, is analogous art.
Applicant argues on pg. 8 of the remarks that Pohlit et al. does not teach or suggest anything regarding polymersomes, and as such, is non-analogous art.
This argument is not persuasive. As discussed in MPEP 2141.01(a), it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. In the instant case, Pohlit et al. teach a method of forming liposomes via dual asymmetric centrifugation (Fig. 1). As such, Pohlit et al. is considered to be reasonably pertinent to the particular problem with which the inventor was concerned and as such, is analogous art.
Conclusion
No claims are allowed.
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 Paul Hoerner whose telephone number is (571)270-0259. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm eastern.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached at (571)272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/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.
/PAUL HOERNER/Examiner, Art Unit 1611
/CRAIG D RICCI/Primary Examiner, Art Unit 1611
Prosecution Insights