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 .
DETAILED ACTION
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 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.
Response to Restriction/Election
Applicant’s amendments filed 3/16/2026 is acknowledged. In the amendments, claims 9-18 and 20 have been canceled and new claims 21-31 have been added and thus claims 1-8 and 21-31 are pending. Applicant’s election without traverse of Group I, claims 1-8 and 19, in response to restriction requirement is acknowledged. New claims 21-31 being directly or indirectly dependent on claims of Group I, are being considered in Group I invention. Applicant’s election of “virus-like particles (VLPs)” as a type or extracellular vesicle, and “membrane protein” as the type of “heterologous protein” in response to election of species requirement is also acknowledged.
Applicants preserve their right to file a divisional on the non-elected subject matter.
Status of the claims
Claims 1-8, 19 and 21-31 are examined on merits in this office action to the extant it encompasses the elected species.
Claim Objections
Claim 1 is objected to because of the following informalities: Abbreviations Acy1.Hrs, ARRDC1 and ARF6 recited in the claim 1 and abbreviation MLGag recited in claim 5 in not proper. Applicant is suggested to spell out the abbreviation the first time it is used in the claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 19 is rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Lu et al. (2018/0055768A1).
In regards to claim 19, Lu teaches producing plurality of extracellular vehicles (EVs) displaying a protein Abstract), comprising
expression of ARRDC1 (paragraph [0093]) and heterologous protein ([0094]; see expression construct encoding polypeptide fused to ARRDC1 wherein the polypeptide comprises fluorescent protein, a kinase, a protease ..; see para [0095]: the cell further comprises a recombinant expression construct encoding a protein; and para [0098]) in a cell.
Culturing the cell in a medium (para [0124]; [0118]); and
Isolating the plurality of EVs comprising the heterologous protein from the medium (para [0018]);
Therefore, the reference is deemed to anticipate the cited claims. Regarding “the cell is a non-adherent cell”, the recitation is recited for an alternative embodiment after “or”.
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 of this title, 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.
Claims 1-8, 19, and 21-31 are rejected under 35 U.S.C. 103 as being obvious over Lu et al. (2018/0055768A1) in view of Qazi et al (Blood 2009; Cite # 48 in the IDS filed 4/8/2025) and Health et al (Scientific Reports 2018).
In regards to claims 1, 3, 4 and 5, Lu teaches producing plurality of extracellular vehicles (EVs) displaying a protein Abstract), comprising
expression of ARRDC1 (paragraph [0093]) and heterologous protein ([0094]; see expression construct encoding polypeptide fused to ARRDC1 wherein the polypeptide comprises fluorescent protein, a kinase, a protease ..; see para [0095]: the cell further comprises a recombinant expression construct encoding a protein; and para [0098]) in a cell.
Culturing the cell in a medium (para [0124]; [0118]); and
Isolating the plurality of EVs comprising the heterologous protein from the medium (para [0018]);
Lu teaches the extracellular vesicles for diagnostic and therapeutic methods (abstract) and for treating diseases (paragraph [0061], [0062]). Lu discloses a reference which teach vesicles as conveyors of immune response (para [0164]).
Lu however, does not disclose using the extracellular vesicles for production of antibody by immunizing an animal with the EVs.
Qazi teaches Exosomes are nanovesicles harboring proteins important for antigen presentation (Abstract). Qazi teaches directly or indirectly loading heterologous protein on exosomes (e.g. ovalbumin; last para of 1st col., page 2674). Isolating exosomes (1st para of 2nd col., page 2674) and immunizing mouse with the exosome preparation (see “Immunization of mice”, 2nd col. of page 2674) and isolating antibody that binds to ovalbumin protein (last para, 2nd col. or page 2674 and last para, 2nd col. of page 2676).
Health teaches extracellular vesicle preparation (Title). Health teaches EVs from different cell lines including HEK293T, H1299, HCT116 and suspension cell Expi293F cells (abstract; 5th paragraph of page 5; and Fig.4).
Therefore, the description in mind of Lu and Qazi and given the fact that exosomes having heterologous protein are useful for immunizing animal for production of antibody against the heterologous protein (Qazi), it would be obvious to one of ordinary skilled in the art to easily envisage utilizing the exosomes obtained from cells expressing heterologous protein of Lu, for immunizing animal with the expectation of developing antibody against the heterologous protein with a reasonable expectation of success. Since Lu teaches various recombinantly expressed proteins in cells and isolating plurality of EVs comprising the heterologous protein from the medium (para [0018]), it would be obvious to envisage the EVs having the expressed proteins for utilizing in the production of antibody against the heterologous protein by immunizing animal in view of Qazi with a reasonable expectation of success.
In regards to non-adherent cells as claimed in claims 2, 3, 21 and 30, Lu in view of Qazi teaches producing antibody against heterologous protein by immunizing animal with EVs produced from cells expressing heterologous protein. Lu teaches various types of cells including HEK293T cells, HeLa cell and A549 cell (paragraphs [0010] and [0012]). Lu does not mention the cells is a non-adherent cell, as for example, 293S or Expi293F cells, as claimed in claims 2, 21 and 30. However, given the fact that Lu teaches different cell types and given the fact that suspension cells Epi293F cells can be utilized for producing EVs and which is an alternative for adherent cell line of 293T (Health), it would be obvious to one of ordinary skilled in the art to easily envisage different types of cells including suspension cells, as for example, Expi293F, for preparation of EVs with a reasonable expectation of success.
In regards to claims 6-7 and 28-29, Lu teaches that heterologous protein can be various proteins including cell surface proteins and membrane protein (para [0031]; [0075]; [0083]; [0104]) among other and thus various heterologous proteins including membrane proteins would be obvious to one of ordinary skilled in the art.
In regards to claims 22 and 31, Qazi teaches isolation of EVs by centrifugation (page 2674, 3rd para of 1st col.) and Lu teaches sucrose density gradient separation of EVs through ultracentrifugation (para [0025] and [0087]) and therefore, separation of EVs utilizing ultracentrifugation is obvious and within the purview of one of ordinary skilled in the art.
In regards to claims 8, 23 and 26, Qazi teaches immunizing mouse and collecting serum at 7 days after primary immunization and 7 days after boosting (page 2675, 2nd col.) and different immunization regimen would be obvious to one of ordinary skilled in the art for optimization.
In regards to claim 24, Lu teaches that direct plasma membrane budding (DPMB) is driven by a specific interaction of TSG101 with a tetrapeptide PSAP motif of an accessory protein, the arrestin-domain-containing protein ARRDC1—which, as described herein, is localized to the plasma membrane through its arrestin domain. The ARRDC1/TSG101 interaction results in relocation of TSG101 from endosomes to the plasma membrane and mediates the release of microvesicles that contain TSG101, ARRDC1, and other cellular components (para [0004]). Lu teaches that in some embodiments, the ARRDC1 protein or fragment thereof comprises an ARRDC1 PSAP domain and in some embodiments, the ARMM further comprises a TSG101 protein or fragment thereof (para [0006]). Lu teaches a model involving ARRDC1-mediated ARMIMs formation and Gag-mediated viral budding wherein both ARRDC1 and Gag interact with TSG101 (para [0021] and Fig. 6). Lu, based on striking parallel between ARRDC1 and Gag in recruitment of TSG101 from the cytosol to the plasma membrane, hypothesized that ARRDC1 may function like Gag to mediate the direct release of plasma membrane-derived vesicles (para [0139]). Lu showed that Gag-GFP and ARRDC1-GFP proteins were robustly present in extracellular vesicles, while the control GFP protein was not, which indicates that Gag can be an alternative for ARRDC1 for providing extracellular vesicles with heterologous protein (para [0139] and [0160]). Therefore, it would be obvious to one of ordinary skilled in the art to easily envisage utilizing MLGag in place of ARRDC1 or including both ARRDC1 and MLGag in the process of producing EVs because Lu teaches that ARRDC1 function like Gag and bote Gag-GFP and ARRDC1-GFP proteins were robustly present in extracellular vesicles.
In regards to claim 25, claim 25 is dependent on claim 8 and claim 8 is rejected for administering a boost to the animal (see the alternative embodiment of claim 8 after “or”) and claim 25 does not limit the process step with administering Ribi adjuvant but only defines the adjuvant of claim 8 and thus is rejected based on claim 8 limitation of “administering a boost”.
In regards to claim 27, as described above Lu teaches EVs comprising various heterologous protein. However, Lu also teaches EVs comprising coding RNA and nucleic acid encoding a protein (para [0008]) and expression construct encoding heterologous protein (para [0010], [0082] and [0095]). Thus, a boost of EVs comprising expression construct of heterologous protein would be obvious to one of ordinary skilled in the art.
Conclusion
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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