DETAILED ACTION
This Office action details a final action on the merits for the above referenced application No. Claims 27, 30-50, and 52-57 are pending in this application.
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
Claims 1-26, 28-29, and 51 are cancelled. Claim 27 is amended.
Response to Amendment
The claim amendments filed on 24 Nov. 2025 have been entered.
Response to Arguments
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) 27, 30-43, 49-50, and 52-57 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2013/052167 A2; published 11 Apr. 2013), in view of Meyer et al. (Small; published 2015) and Lai et al. (RSC Adv.; published 2015) for the reasons cited in the Office action filed on 23 May 2025.
Claim(s) 27, 30-50 and 52-57 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2013/052167 A2; published 11 Apr. 2013), in view of Meyer et al. (Small; published 2015) and Lai et al. (RSC Adv.; published 2015), in further view of Salzman et al. (US 7,534,449 B2; issued 19 May 2009) for the reasons cited in the Office action filed on 23 May 2025.
Applicants Arguments
Applicants assert that extensive experimentation was required to arrive at the claimed invention. As evidenced in Fig. 2, the prolate ellipsoidal particles were not coated with macrophage membranes using the extrusion method taught by Zhang. The process disclosed by Zhang in view of Meyer and Lai could not be used to arrive at the claimed invention. In Zhang, PLGA nanoparticles were fused with RBC membrane-derived vesicles through mechanical extrusion as shown in Fig. 1. The mechanical force facilitated the sub-100 nm PLGA nanoparticles to cross the lipid bilayers resulting in vesicle particle fusion. In contrast to Zhang, it was found that an extrusion process was not suitable to prepare supported biomimetic membranes on anisotropic particles due to non-uniform coating. Zheng is silent about forming ellipsoidal particles. Extensive experimentation was required to achieve coating of ellipsoidal particles with naturally derived membranes and that membrane-coated anisotropic particles could not be prepared by the method of Meyer. Lai is directed to superparamagnetic iron oxide nanoparticles and the particles in Lai are designed to enhance cellular uptake whereas the instantly claimed particles are designed to reduce cellular uptake. Meyer and Saltzman do not cure the defects. Applicants assert unexpected results. The data at Fig. 6 of the Green declaration demonstrate that not only did the membrane coated ellipsoidal particles resist unwanted phagocytic uptake, but that the synergy of combining ellipsoidal shape with membrane led to much larger beneficial effect that what was expected. At Fig. 10 of the Green declaration, prolate and oblate ellipsoidal particles showed significantly greater killing compared to spherical particles.
Applicant's arguments filed 24 Nov. 2025 have been fully considered but they are not persuasive. In one embodiment at pg. 47, Zhang provides for RBC-coated PLGA nanoparticles having a size of about 70 nm and wherein the RBC coated PLGA nanoparticles are suitable for diagnostic and therapeutic application by incorporation of a dye (DiD) or therapeutic agent (DOX). At the examples, the membrane coated nanoparticles are understood to have a spherical shape. At pg. 47 the RBC coated were prepared by extrusion of PLGA nanoparticles and RBC membrane derived vesicles through a porous polycarbonate membrane. Regarding particle shape, Zhang at several places teaches that the particles can be any suitable shape including disc and circular cylinder shapes. At pg. 54, Zhang teaches extending particle residence time in vivo by modifying the shape of the NPs. At reference 5, Zhang teaches the shape effects of filaments versus spherical particles in flow and drug deliver applications. In this case, Zhang alone provides adequate reason and motivation for one of ordinary skill in the art modify the shape of the RBC coated PLGA nanoparticles therein to arrive at an anisotropic shape wherein at least one of a x-, y-, and z-axis are not equal in order to advantageously extend the residence time of the nanoparticles in vivo. Regarding the synthesis method used by Zhang to prepare the RBC coated PLGA nanoparticles, first, it is noted that none of the claims are directed to a synthesis method – claim 1 merely requires a biomimetic particle comprising a three-dimensional microparticle or nanoparticle and a naturally derived cell membrane selected from RBC or platelet. Second, the Green declaration points to a Fig. 2 that states that although the same protocol was applied to successfully coat spherical particles, the coating did not work on anisotropic particles. However, it is unclear from Fig. 2 if not a single particle was coated. A single membrane coated particle having an ellipsoidal shape is all that is required to meet claim 1. Still further, the protocol applied at Fig. 2 is unclear and the anisotropic shape is unclear. Instant Fig. 23 shows biodegradable particles coated with a cell membrane via an extrusion process. The membrane coating is not uniform using a co-extrusion process. However, claim 1 does not require uniform membrane coating. Only a single RBC or platelet coated microparticle and nanoparticle having an ellipsoidal shape is required to meet claim 1. Meyer provides reason and motivation to modify the shape of the particles taught by Zhang to arrive at particles having an ellipsoidal shape. Meyer teaches that the advantages of ellipsoidal aAPC compared to spherical aAPC as seen in vitro including superior T-Cell stimulation, reduced non-specific uptake and better half-life/distribution upon systemic injection. A recognized advantage is the strongest reason to combine. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Zhang so that for example the RBC coated PLGA nanoparticles having an ellipsoidal shape because the ellipsoidal shape would have been expected to advantageously enable reduced non-specific uptake and better half-life distribution upon systemic injection.
At for example pg. 7, Zhang teaches acoustical energy exerted by sonification method as the next available method for make the membrane coated nanoparticles of the invention including RBC coated PLGA nanoparticles. Regarding applicant’s argument that Lai teaches SPIO nanoparticles, it is noted that claim 1 does not limit the microparticle or nanoparticle material. Lai successfully prepared cell membrane coated nanoparticles for biomedical application by the sonification method characterized as simple and mild. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Zhang so that the RBC coated PLGA nanoparticles having an anisotropic shape get prepared by the sonification method because the sonification method would have been expected to advantageously enable a simple and mild preparation of the RBC coated PLGA nanoparticles having an anisotropic shape.
Regarding applicants’ assertion of unexpected results, it noted that the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. See In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). While claim 1 has been amended to by narrowing the radius of curvature along at least one axis and by limiting the cell membranes to RBC and platelet membranes, the claim does not limit size of the particles or particle material. Fig. 6 of the Green declaration shows that prolate and oblate ellipsoid coated particles were phagocytosed significantly less that their uncoated counterparts and oblate ellipsoidal particles were phagocytosed significantly less than spherical particles. However, Fig 6 does not provide any characterization of the particles used in the experiments including particle material and particle size. The particle material can affect the density of the particle having an effect on distribution and macrophage cell uptake. The particle size can similarly affect distribution and macrophage uptake. Claim 39 further limits the biomimetic particle ranges in size; however, the range is wide and the information at Fig. 6 does not allow a determination of whether the results occur over the range claimed in claim 9. Expected beneficial results are evidence of obviousness. See In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967). At for example 1525, Meyer teaches that ellipsoidal nanoparticles offer reduced cellular uptake by macrophages and endothelial cells in vitro and resist hepatic and splenic elimination in vivo. At pg. 43, Zhang teaches that the RBC membrane coated nanoparticles have longer elimination half-life. The nanoparticle modified with functional components on the RBC membranes contain immunosuppressive proteins the inhibit macrophage uptake. Accordingly, a person of ordinary skill in the art would have expected membrane coated particles to be phagocytosed significantly less than their counterpart and phagocytosed than spherical particles.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618