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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 18-30 drawn to methods of delivering RSVF-containing exosomes to cancer cells in the reply filed on 4/17/2026 is acknowledged. The traversal is on the grounds that the Examiner has not properly identified the shared special technical feature shared amongst the group and use of the Chahar publication as evidence of a lack of unity of invention was inappropriate. The Applicant submits the following:
The mere fact that the exosomes induce cytokine release in Chahar’s findings does not mean that they deliver anticancer agents to cancer cells, thus the interpretation of anticancer agents is overly broad;
The exosomes of Chahar have no infectivity;
There is no disclosure as to whether the F protein is contained inside or outside the exosome, nor is there any disclosure regarding specific fusion with cancer cells.
This is not found persuasive, because the technical feature that links all of the inventions is the product of claim 31, which is an exosome both expressing RSVF on its surface and comprising an anticancer agent. An exosome both expressing RSVF on its surface and comprising an anticancer agent would be indistinguishable from the product of Chahar based on their features comprising the RSV fusion protein F and signals that induce a proinflammatory response, thus triggering apoptosis in recipient cells. Since the instant disclosure defines that “the anticancer agent may be used without limitation as long as it is known in the art” (page 14, ¶ 6), and since agents inducing cytokine release that may lead to apoptosis satisfy the broadest reasonable interpretation of “anticancer agents”, Chahar effectively teaches the shared technical feature of an exosome comprising RSVF and anticancer agents.
The requirement is still deemed proper and is therefore made FINAL.
Claims 18-35 are pending in the instant application.
Claims 18-30 are being examined on the merit.
Claims 31-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 4/17/2026.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Information Disclosure Statement
Applicant’s IDS submitted 5/26/2023 has been acknowledged and considered.
Signed copies are attached hereto.
Specification
The use of the term Lipofectamine-TM, Zetasizer®, VitrobotTM which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. All trademarks referenced herein should be identified as such with the appropriate notation:
Lipofectamine (page 16, line 1);
Zetasizer (page 17, fifth paragraph);
Vitrobot (page 18, second paragraph).
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 19-20, 26-28, and 31 are objected to because of the following informalities:
Claims 19-20, 26-28, and 31 contains a typo. “RSFV” should read “RSVF”. Appropriate correction is required.
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.
Claims 18 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (Kim et al, WO2019066535A1, Priority to 9/28/2017, Published on 4/4/2019; hereinafter Kim), and further in view of Canedo-Marroquin (Canedo-Marroquin et al, “Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity”, August 16, 2017, Front Cell Infect Microbiol, 7(367):1-10; hereinafter Canedo-Marroquin).
Regarding instant claims 18 and 25, Kim teaches exosomes comprising a modified VSV-G protein in the membrane of the exosome, and one or more immunogenic cell death inducers, wherein the immunogenic cell death inducer is an anthracycline-based anticancer agent (page 7, ¶ [46]-[47], [50], [52]). Kim also teaches a pharmaceutical composition for the treatment of cancer comprising administering the exosome as an active ingredient, wherein a virus-derived membrane fusion protein is introduced to the membrane of the exosome (page 7, ¶ [53]-[54]; page 8, ¶ [62]). Furthermore, Kim discloses that the pharmaceutical composition may further comprise anticancer compounds, wherein the anticancer compound may be encapsulated inside the plasma membrane-based vesicle. (page 7, ¶ [56] – page 8, ¶ [57]-[58]). Kim discloses that the recombinant exosome comprising the modified VSV-G protein on the surface of the exosome (mVSVG-Exo) induced membrane fusion of cancer cells at pH 6.8 (page 9, ¶ [69]). Kim further discloses that a virus-derived membrane fusion protein other than the VSV-G protein may also exhibit an effect similar to that of the wtVSVG exosome or the mutantVSVG exosome used herein (page 10, ¶ [72]).
However, Kim does not teach a method of delivering anticancer agents in an exosome to cancer cells, wherein the exosomes comprise a respiratory syncytial virus F protein (RSVF).
The deficiency is resolved by Canedo-Marroquin.
Canedo-Marroquin teaches that human Respiratory Syncytial Virus (hRSV) comprises a fusion protein (F), which is a transmembrane protein that is required for hRSV fusion and entry into the host cell. Canedo-Marroquin also discloses that the entry mechanism of hRSV is pH, clathrin, and dynamin independent, Further, Canedo-Marroquin also teaches that the F protein interacts with nucleolin, a ubiquitous host receptor (page 2, right column, last paragraph – page 3, left column).
Regarding instant claims 18 and 25, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the pharmaceutical composition comprising the exosomes, wherein the exosomes comprise a modified VSV-G protein in the membrane of the exosome and an anticancer agent encapsulated inside the plasma membrane-based vesicle as taught by Kim and substitute VSVG with RSVF as taught by Canedo-Marroquin. This is obvious because, Kim teaches pharmaceutical compositions comprising exosomes for the treatment of cancer, wherein the exosomes comprise a modified VSV-G protein in the membrane of the exosome, and one or more immunogenic cell death inducers (e.g. anticancer agents) encapsulated inside the plasma membrane-based vesicle wherein the recombinant exosome comprising the modified VSV-G protein on the surface of the exosome induced membrane fusion with cancer cells, and Canedo-Marroquin teaches that hRSV comprises a F protein that is required for hRSV fusion and entry into the host cell, wherein the entry mechanism of hRSV is pH, clathrin, and dynamin independent. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant pharmaceutical composition comprising the instant exosome or instant method of delivering anticancer agents in the instant exosome to cancer cells, wherein the instant exosome comprises fusing membrane between the instant exosome including RSVF and a plasma membrane of the cancer cells.
Claims 19-21 and 26-30 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (Kim et al, WO2019066535A1, Priority to 9/28/2017, Published on 4/4/2019; hereinafter Kim), and Canedo-Marroquin (Canedo-Marroquin et al, “Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity”, August 16, 2017, Front Cell Infect Microbiol, 7(367):1-10; hereinafter Canedo-Marroquin), as applied to claim 18 above, and further in view of Tayyari (Tayyari et al, “Identification of nucleolin as a cellular receptor for human respiratory syncytial virus”, August 14, 2011, Nature Medicine, 17(9):1132-1136; hereinafter Tayyari), and Wu (Wu et al, “Phosphorylation and changes in the distribution of nucleolin promote tumor metastasis via the PI3K/Akt pathway in colorectal carcinoma”, May 21, 2014, FEBS Letters, 588(10):1921-1929; hereinafter Wu).
The combined teachings of Kim and Canedo-Marroquin are discussed above.
Additionally, Kim discloses that the recombinant exosome comprising the modified VSV-G protein on the surface of the exosome (mVSVG-Exo) promoted phagocytosis of various cancer cell types (e.g. 4T1-Luc breast cancer cells, EL4-Ova lymphoma cells, and CT26.CL25 colon cancer cells) by macrophages and dendritic cells, wherein the VSVG acted as a TLR4 agonist as shown in FIG. 9, suggesting that the recombinant exosomes are multifunctional anticancer agents exhibiting anticancer activity through various mechanisms (page 9, ¶ [69]; FIGs. 8A-8C and 9; Example 3).
However, the combined teachings of Kim and Canedo-Marroquin do not teach a method of delivering anticancer agents in an exosome to cancer cells comprising fusing membrane between the exosome including RSVF and the plasma membrane of the cancer cells, wherein fusing membrane is due to the interaction between the RSVF expressed on the outside of the exosome and nucleolin on the surface of the cancer cells.
The deficiency is resolved by Canedo-Marroquin, Tayyari and Wu.
Furthermore, Canedo-Marroquin also discloses that the F protein interacts with the TLR-4 to activate the receptor, herein initiating an antiviral immune response (page 4, left column, third paragraph).
Tayyari teaches that nucleolin, a ubiquitous molecule with many reported functions, including ligand binding, is a RSV receptor molecule, wherein RSV directly binds to nucleolin on the cell surface (shown by colocalization studies as described in Figure 2) (pages 1132-1133; Figures 1 and 2). Tayyari also teaches that the mechanism by which RSV and nucleolin interacts is that the RSV binding to surface proteoglycans, such as nucleolin, stabilize the virion to enable engagement of the RSV fusion protein (RSVF) with nucleolin on the target cell surface, similar to the cellular receptors of other enveloped viruses, e.g. herpes simplex virus and hepatitis B virus (page 1134, right column, last paragraph – page 1136, left column, first paragraph).
Wu teaches that nucleolin is a multifunctional protein, wherein cell surface nucleolin plays an important role in migration and capillary-tubule formation. Wu also discloses that targeting nucleolin on the plasma membrane of cancer cells seems to be an effective approach to inhibit cancer cell growth and angiogenesis, suggesting that cell surface nucleolin may be a novel cancer therapy target (page 1921, left column, second paragraph – right column, first paragraph). Wu also discloses that while the expression levels of total nucleolin was not different between the adenocarcinoma group and the metastases group (Fig. 4), inhibition of cell surface nucleolin inhibited the process of epithelial mesenchymal transitions (EMT) in colon cancer cells, suggesting that the distribution of nucleolin was related to metastatic potential (page 1928, right column, fourth and fifth paragraph; page 1921, Abstract).
Regarding instant claims 19-21, 26-27, and 29-30, it would have been obvious for a person having ordinary skill in the art at the time of filing to modify the pharmaceutical composition comprising an exosome, wherein the exosome comprises RSVF and anticancer agents that fuse membrane between the exosome and the plasma membrane of cancer cells as taught by the combined teachings of Kim and Canedo-Marroquin to further comprise that the fusing membrane is due to the interaction between the RSVF expressed on the outside of the exosome and nucleolin expressed on the surface of cancer cells as taught by Tayyari, e.g. colon cancer cells as taught by Wu. This is obvious because, the combined teachings of Kim and Canedo-Marroquin teach pharmaceutical compositions comprising exosomes for the treatment of cancer, wherein the exosomes comprise a RSVF protein in the membrane of the exosome, and anticancer agents wherein the recombinant exosome induce membrane fusion with cancer cells, Tayyari teaches that nucleolin is a RSV receptor molecule, wherein RSV directly binds to nucleolin on the cell surface for stabilization, and Wu teaches that cell surface nucleolin plays an important role in cancer cell growth and angiogenesis, wherein inhibition of cell surface nucleolin inhibited the process of EMT in colon cancer cells. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant pharmaceutical composition comprising the instant exosome or instant method of delivering anticancer agents in the instant exosome to cancer cells, wherein the instant exosome comprises fusing membrane between the instant exosome including RSVF expressed on the outside of the instant exosome and nucleolin on the surface of the plasma membrane of cancer cells, such as colon cancer cells.
Regarding instant claim 28, it would have been obvious for a person having ordinary skill in the art at the time of filing to modify the pharmaceutical composition for the treatment of cancer comprising administering an exosome comprising RSVF and anticancer agents, wherein the RSVF of the exosome interacts with the RSV receptor nucleolin on the surface of the plasma membrane of cancer cells to induce fusion between the exosome and cancer cell as taught by the combined teachings of Kim, Canedo-Marroquin, Tayyari, and Wu to further comprise that the RSVF induces phagocytosis of the cancer cells through host immune activation as taught by Kim and Canedo-Marroquin. This is obvious because, the combined teachings of Kim and Canedo-Marroquin teach exosomes and pharmaceutical compositions comprising exosomes for the treatment of cancer, wherein the exosomes comprise a RSVF protein in the membrane of the exosome, and anticancer agents wherein the recombinant exosome induce membrane fusion with cancer cells, Kim further teaches that mVSVG-Exo promoted phagocytosis of various cancer cell types (e.g. 4T1-Luc breast cancer cells, EL4-Ova lymphoma cells, and CT26.CL25 colon cancer cells) by macrophages and dendritic cells, wherein the VSVG acted as a TLR4 agonist, Canedo-Marroquin further discloses that the F protein of hRSV interacts with TLR-4 to activate the receptor, herein initiating an antiviral immune response, Tayyari teaches that nucleolin is a RSV receptor molecule, wherein RSV directly binds to nucleolin on the cell surface for stabilization, and Wu teaches that cell surface nucleolin plays an important role in cancer cell growth and angiogenesis, wherein inhibition of cell surface nucleolin inhibited the process of EMT in colon cancer cells. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant cancer therapeutic method comprising delivering the anticancer agents in the instant exosome to cancer cells, wherein the RSVF of the instant exosome is delivered to a cancer cell membrane through fusion with the plasma membrane of cancer cells by mediating the instant exosome by nucleolin as a receptor on the surface of cancer cells, inducing phagocytosis of the cancer cells through host immune activation.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Kim (Kim et al, WO2019066535A1, Priority to 9/28/2017, Published on 4/4/2019; hereinafter Kim), and Canedo-Marroquin (Canedo-Marroquin et al, “Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity”, August 16, 2017, Front Cell Infect Microbiol, 7(367):1-10; hereinafter Canedo-Marroquin) as applied to claim 18 above, and further in view of Wang (Wang et al, “The unfolded protein response as a target for anticancer therapeutics”, May 7, 2018, Critical Reviews in Oncology/Hematology, 127:66-79; hereinafter Wang).
The combined teachings of Kim and Canedo-Marroquin are discussed above.
However, the combined teachings of Kim and Canedo-Marroquin do not teach an exosome comprising RSVF and anticancer agents wherein the anticancer agents are unfolded proteins.
The deficiency is resolved by Wang.
Wang teaches that ER stress is initiated when the unfolded or misfolded protein load exceeds the capacity of the ER to properly fold protein, and while cancer cells can tolerate mild ER stress, persistent and severe ER stress kills cancer cells by inducing their autophagy, apoptosis, necroptosis, or immunogenic cell death (page 66, Abstract, pathway described in Fig. 2). As a result, anticancer drugs that induce ER stress in cancer cells have been developed, such as the small molecule HA15, which targets GRP78 to trigger concomitant ER stress-induced apoptosis and autophagy in cancer cells, wherein HA15 induces a very strong autophagy signal through vesicle accumulation, early autophagosome sequestering in cytosol, and a high percentage of conversion of LC3-I to LC3-II. Wang also discloses that inhibition of either autophagy or apoptosis reduced the treatment efficiency of HA15, suggesting that autophagy induction aids in cancer treatment (page, §3.1, last paragraph).
Regarding instant claim 22, it would have been obvious for a person having ordinary skill in the art at the time of filing to modify the exosome comprising RSVF and anticancer agents that fuse membrane between the exosome and the plasma membrane of cancer cells as taught by the combined teachings of Kim and Canedo-Marroquin to further comprise that the anticancer agents are unfolded proteins as taught by Wang. This is obvious because, the combined teachings of Kim and Canedo-Marroquin teach pharmaceutical compositions comprising exosomes for the treatment of cancer, wherein the exosomes comprise a RSVF protein in the membrane of the exosome, and anticancer agents wherein the recombinant exosome induce membrane fusion with cancer cells, and Wang teaches that ER stress is induced when the unfolded or misfolded protein load exceeds the capacity of the ER to properly fold protein, wherein while cancer cells can tolerate mild ER stress, persistent and severe ER stress kills cancer cells by inducing their autophagy, apoptosis, necroptosis, or immunogenic cell death. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant method of delivering anticancer agents in an exosome to cancer cells, comprising fusing membrane between the exosome including RSVF and a plasma membrane of the cancer cells, wherein the instant anticancer agents are unfolded proteins.
Claims 23 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (Kim et al, WO2019066535A1, Priority to 9/28/2017, Published on 4/4/2019; hereinafter Kim), Canedo-Marroquin (Canedo-Marroquin et al, “Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity”, August 16, 2017, Front Cell Infect Microbiol, 7(367):1-10; hereinafter Canedo-Marroquin), and Wang (Wang et al, “The unfolded protein response as a target for anticancer therapeutics”, May 7, 2018, Critical Reviews in Oncology/Hematology, 127:66-79; hereinafter Wang) as applied to claim 18 above, and further in view of Benbrook (Benbrook and Long, “Integration of Autophagy, Proteosomal Degradation, Unfolded Protein Response And Apoptosis”, June 15, 2012, Exp Oncol, 34(3): 286-297; hereinafter Benbrook) and Yuan (Yuan et al, “Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia”, March 2015, Haematologica, 100(3):345-356; hereinafter Yuan).
The combined teachings of Kim, Canedo-Marroquin, and Wang are discussed above.
However, the combined teachings of Kim, Canedo-Marroquin, and Wang do not teach a method of delivering anticancer agents in an exosome to cancer cells comprising fusing membrane between the exosome including RSVF and a plasma membrane of the cancer cells, wherein the anticancer agents are unfolded proteins that are accumulated inside the exosome due to inhibition of phagosome-lysosome fusion by treatment with a phagosome-lysosome fusion inhibitor, wherein the inhibition of phagosome-lysosome fusion by the phagosome-lysosome fusion inhibitor is induced by any one selected from the group consisting of promotion of vacuolar type H+ ATPase, inhibition of proteasome function, inhibition of autophagosome formation, and deacetylase inhibition.
The deficiency is resolved by Benbrook and Yuan.
Benbrook teaches that HDAC6, a microtubule-associated acetylase, binds to and utilizes dynein motors to transport ubiquitinated proteins along microtubules to a structure called the aggresome, where they are recognized by developing autophagosomes. Benbrook also teaches that fusion with lysosomes is mediated by dynein transportation of these autophagosomes along microtubules to fuse with endosomes or lysosomes for degradation for re-utilization in cellular metabolism. Consequently, Benbrook teaches that inhibition of lysosomal acidification by Bafilomycin A1, a specific V-ATPase (vacuolar H+ ATPase) inhibitor, or by other lysosomal function inhibitors, such as CQ (Chloroquine) and HCQ (hydroxychloroquine), will cause accumulation of autophagosomes and unfolded proteins (page 288, right column, third paragraph, For pathway, see Figure 2).
Yuan teaches that bafilomycin A1 has been used in various studies of autophagy as an inhibitor of fusion between autophagosomes and lysosomes and as an inhibitor of lysosomal degradation. Yuan also discloses that bafilomycin A1 inhibits cell growth and induces apoptosis and differentiation, wherein these anticancer effects of bafilomycin A1 are considered attributable to the intracellular acidosis caused by V-ATPase inhibition (page 345, left column, second paragraph – right column (continued)). Yuan discloses that bafilomycin A1 attenuates cytoprotective autophagy, induces apoptosis, and delays the onset of leukemia in a xenograft mouse model and inhibits and kills leukemic primary cells (page 345, Abstract; page 346, left column, second paragraph).
Yuan also discloses that unlike other drugs, bafilomycin A1 inhibits and kills pediatric B-ALL cells at multiple targets while sparing normal cells. Yuan further teaches that bafilomycin a1 not only targets early autophagy signaling, but also targets H-ATPase of lysosomes and blocks late-phase autophagy activity. Furthermore, bafilomycin a1 targets mitochondria to activate the AIF-dependent apoptotic cell death pathway and promotes Beclin 1 binding to Bcl-2, further decreasing cytoprotective autophagy and activating apoptotic cell death (page 354, right column, last paragraph – page 355, left column). Yuan concludes that whereas apoptosis is implicated in the removal of damaged or unwanted cells, autophagy is a cellular catabolic pathway that is involved in lysosomal degradation and recycling of proteins and organelles, and is therefore considered as an important survival mechanism for both normal cells and cancer cells in response to metabolic stress or chemotherapy (page 345, right column, second paragraph).
Regarding instant claims 23 and 24, it would have been obvious for a person having ordinary skill in the art at the time of filing to modify the exosome comprising RSVF and anticancer agents that fuse membrane between the exosome and the plasma membrane of cancer cells, wherein the anticancer agents are unfolded proteins as taught by the combined teachings of Kim, Canedo-Marroquin, and Wang to further comprise that the unfolded proteins are accumulated inside exosome due to inhibition of phagosome-lysosome fusion by treatment with the phagosome-lysosome fusion inhibitor as taught by Benbrook, wherein the phagosome-lysosome fusion inhibitor is bafilomycin a1, an inhibitor of vacuolar type H+ ATPase as taught by Yuan. This is obvious because, the combined teachings of Kim, Canedo-Marroquin, and Wang teach pharmaceutical compositions comprising exosomes for the treatment of cancer, wherein the exosomes comprise a RSVF protein in the membrane of the exosome, and unfolded proteins as anticancer agents wherein the recombinant exosome induce membrane fusion with cancer cells to induce ER stress when the unfolded protein load exceeds the capacity of the ER to properly fold protein, thereby killing cancer cells by inducing their autophagy or apoptosis, Benbrook teaches inhibition of lysosomal acidification by bafilomycin A will cause accumulation of autophagosomes and unfolded proteins, and Yuan teaches bafilomycin A1 inhibits cell growth and induces apoptosis and differentiation in cancer cells, wherein these anticancer effects of bafilomycin A1 are considered attributable to the intracellular acidosis caused by V-ATPase inhibition. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant method of delivering anticancer agents in an exosome to cancer cells, comprising fusing membrane between the exosome including RSVF and a plasma membrane of the cancer cells, wherein the instant anticancer agents are unfolded proteins, wherein the unfolded proteins are accumulated inside the instant exosome due to inhibition of phagosome-lysosome fusion by treatment with a vacuolar type H+ ATPase inhibitor.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jieun Ham whose telephone number is (571)272-7779. The examiner can normally be reached Monday - Friday 7-2.
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/J.H./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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