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 .
Claims 1-18 are pending. Claims 10-18 are withdrawn. Claims 1-9 are under examination.
Election/Restrictions
Applicant’s election without traverse of Group I claims 1-9 in the reply filed on 06/22/2026 is acknowledged.
Claims 10-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/22/2026.
Claim Objections
Claims 3 and 4 are objected to because of the following informalities: Please insert a space between RPMI and 1640 in claim 3. Please spell out the full meaning of DSPE-PEG-FA in claim 3. Please insert a space between Raw and 264.7 in claim 4. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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.
Claims 1-2, 4 and 8 is/are rejected under 35 USC 102 (a)(1) as being anticipated by Yan et al. J Nanobiotechnol (2020) 18:115 https://doi.org/10.1186/s12951-020-00675-6.
Claim 1: Yan et al disclose a method for preparing cell microparticles (exosomes) capable of targeting Folr2+ macrophages, comprising the step of extracting the exosomes from the macrophages. See page 2-3 under isolation and characterization of exosomes.
Claim 2: Yan et al disclose the method according to claim 1, comprising the following steps:
S1: culturing RAW 264.7 macrophages to obtain a macrophage culture;
S2: extracting the exosomes from the macrophage culture. See page 2-3 under isolation and characterization of exosomes.
Claim 4: Yan et al disclose the method according to claim 2, wherein the macrophage cell is Raw264.7. See page 2-3 under isolation and characterization of exosomes.
Claim 8: Yan et al disclose the method according to claim 1, further comprising the step of co-incubating the cell microparticles with a drug wherein the drug is dexamethasone. See page 3 under preparation of ExoDex and FPC-Exo/Dex.
Claims 1-3 and 8 is/are rejected under 35 USC 102 (a)(1) as being anticipated by
Zhang et al. ACS Nano 2017, 11, 277−290.
Claim 1: Zhang et al disclose a method for preparing cell microparticles (microvesicles MV) capable of targeting Folr2+ macrophages (THP-1 cell derived macrophages), comprising the step of extracting the MVs from the macrophages. See page 287 under cell culture and treatment.
Claim 2: Zhang et al disclose the method according to claim 1, comprising the following steps:
S1: culturing the THP-1 macrophages to obtain a macrophage culture;
S2: extracting the MV from the macrophage culture i.e. THP-1 cells were induced into macrophages and purified from supernatants of the macrophage culture. See page 287 under cell culture and treatment and under generation and purification of MVs.
Claim 3: Zhang et al disclose the method according to claim 2, wherein in S1, the macrophages are cultured in RPMI 1640 medium supplemented with DSPE-PEG-FA. See page 287 under cell culture and treatment and under generation and purification of MVs.
Claim 8: Zhang et al disclose the method of claim 1, further comprising the step of co-incubating the MVs with the drug doxorubicin. See DOX Loading and Intracellular Release from FA/IONP-MVs on page 288.
Claims 1-2 and 4-8 is/are rejected under 35 USC 102 (a)(1) as being anticipated by Gan et al. CN 109893515A 06-18-2019.
Claim 1: Gan et al disclose a method for preparing cell microparticles capable of targeting Folr2+ macrophages, comprising the step of extracting the microparticles from Raw 264.7 macrophages. See example 1 mannose-modified macrophage medicine carrying micro-particle preparation and characterization.
Claim 2. Gan et al disclose the method according to claim 1, comprising the following steps:
S1: culturing Raw 264.7 macrophages to obtain a macrophage culture;
S2: extracting cell microparticles from the macrophage culture. See example 1 mannose-modified macrophage medicine carrying micro-particle preparation and characterization.
Claim 4. Gan et al disclose the method according to claim 2, wherein the macrophage cell is Raw 264.7. See example 1 mannose-modified macrophage medicine carrying micro-particle preparation and characterization.
Claim 5. Gan et al disclose the method according to claim 2, wherein S2 comprises the following steps:
S21: subjecting the macrophage culture to ultraviolet irradiation (irradiating for 60 min by ultraviolet); and
S22: extracting the cell microparticles from the macrophage culture after ultraviolet irradiation. See experimental step under example 1 mannose-modified macrophage medicine carrying micro-particle preparation and characterization.
Claim 6. Gan et al disclose the method according to claim 5, wherein S21 comprises the following steps:
S211: resuspending the macrophage culture with serum-free medium to obtain a cell suspension (when the cell amount reaches 5 X 107, removing the culture medium and washing with phosphate buffer solution (PBS), then adding 4 mL of serum-free DMEM culture medium);
S212: subjecting the cell suspension to ultraviolet irradiation for 1h ( irradiating for 60 min(1 hr) by ultraviolet) and
S213: allowing the cell suspension to stand at 37°C for over 10h (24 hours). See under "1. Experimental Materials and reagent Raw 264.7 mouse macrophages using the same embodiment, H22 mouse liver cancer cell the same as embodiment 2, metformin and a 3 D soft fibrin gel is commercially available".
7. Gan et al disclose the method according to claim 6, wherein S22 comprises the following steps:
S221: performing low-speed centrifugation on the cell suspension to obtain a supernatant containing cell microparticles (24h after administration of metformin, executing separation to macrophage apoptosis taking the supernatant for centrifuging gradually, at a rotating speed of 200g, 600g after each centrifuging for 10min to 14000g centrifugal force for 1min, to remove cells and debris);
S222: subjecting the supernatant containing cell microparticles to high-speed centrifugation to obtain a cell microparticle precipitate (taking the drug microparticles (Met Man-MPs) of centrifugal supernatant after centrifugal 1h further at a centrifugal force of 20000g, obtaining macrophage apoptosis produced by the mannose modified, as the experimental group); and
S223: resuspending the cell microparticle precipitate to obtain the cell microparticle (the obtained microparticles dissolved in PBS). See under Example 1 mannose-modified macrophage medicine carrying micro-particle preparation and characterization.
8. Gan et al disclose the method according to claim 1, further comprising the step of co-incubating the cell microparticles with a drug e.g. metformin hydrochloride. See under Example 1 mannose-modified macrophage medicine carrying micro-particle preparation and characterization.
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 1 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Gan et al. CN 109893515 06-18-2019 in view of Yang et al. CN 107693489 02-16-2018
Claim 1: Gan et al disclose a method for preparing cell microparticles capable of targeting Folr2+ macrophages, comprising the step of extracting the microparticles from RAW 264.7 macrophages. See example 1 mannose-modified RAW 264.7 macrophage medicine carrying micro-particle preparation and characterization.
Claim 8: Gan et al disclose the method according to claim 1, further comprising the step of co-incubating the cell microparticles with a drug. See abstract and technical field.
Gan et al disclose the cell vesicles derived from macrophage can be used to deliver drugs and can be used for targeted drug delivery and disclose they have low immunogenicity, good in vivo long circulating property and high cell targeting to tumor associated macrophages thereby enhancing the M2 tumour-associated macrophages of reverse polarization, recovery macrophages for tumor cell killing ability, improve the tumor micro-environment and improve anti-tumour effect. See abstract, background of the invention and summary of the invention.
Gan et al does not disclose the drug is a chlorophosphate.
Yang et al disclose the use of microparticles to deliver chlorine phosphonic acid disodium (Clodronate) a chlorophosphate to macrophages for treating enteritis and preventing the occurrence of colorectal cancer. See abstract.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have modified the method of Gan et al such that the drug by delivered by cell-derived microparticles is a chlorophosphate such as chlorine phosphonic acid disodium (Clodronate), thus resulting in the instant invention with a reasonable expectation of success.
The motivation to do so is that Yang et al disclose that microparticles can be used to deliver chlorine phosphonic acid disodium (Clodronate) a chlorophosphate to macrophages for treating enteritis and preventing the occurrence of colorectal cancer and Gan et al disclose that the cell vesicles derived from macrophage can be used to deliver drugs and can be used for targeted drug delivery and disclose they have low immunogenicity, good in vivo long circulating property and high cell targeting to tumor associated macrophages thereby enhancing the M2 tumour-associated macrophages of reverse polarization, recovery macrophages for tumor cell killing ability, improve the tumor micro-environment and improve anti-tumour effect.
Status of Claims
Claims 10-18 are withdrawn. Claims 1-9 are withdrawn.
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/OLUWATOSIN A OGUNBIYI/Primary Examiner, Art Unit 1645
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