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
Status of Application/Election/Restrictions
Applicant’s election of Group I (claims 1-11), mesenchymal stem cells for species of source, organic molecule for species of active molecule and vitamin D for species of redoxome and desferrioxamine (DFX) for species of iron chelator in the reply filed on September 21, 2022 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-23 are pending. Claims 12-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was treated as without traverse in the reply filed on September 21, 2022.
Claims 1-11 are under examination with respect to mesenchymal stem cells, organic molecule, vitamin D and desferrioxamine (DFX) in this office action.
Specification
The disclosure is objected to because of the following informalities: The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see p. 19). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Appropriate correction is required.
The use of the term “NanoDrop” (p. 32; p.48), “ZetaSizer” (p. 33), “NanoSight” (p. 33), “BODIPY” (p. 34), “SpeedVac” (p.36), “Zeist” (p. 36), “Gene Pulser Xcell”, “OptiMEM” (p.42), “Glutamax” (p.44), “BioDipy” (p. 46), ”, 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.
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. Appropriate correction is required.
Claim Objections
6. Claims 3, 4 and 7 are is objected to because of the following informalities: “GI”, “CoQ10”, “LPO” is not a common abbreviation in the art. Applicants are required to spell out “GI”, “CoQ10”, “LPO” at the first usage. Appropriate correction is required.
7. Claims 12-23 are objected to because of the following informalities: the status of the claims 12-23 is incorrect because these claims are withdrawn from consideration. Appropriate correction is required.
See MPEP 714 & 37 CFR 1.121.
“In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).”
Improper Markush Grouping
8. Claims 3-4 and 6-8 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y).
The Markush grouping of different types of cells, tissues, fluids and medium recited in claim 3, different agents, peptides, antibodies, compounds, blockers, acids, iron chelators and molecules recited in claims 4 and 6-8 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The recited alternative species do not share a single structural similarity. Each type of cells, tissues, fluids and medium recited in claim 3 or each type of agents, peptides, antibodies, compounds, blockers, acids, iron chelators and molecules recited in claims 4 and 6-8 has a different chemical structure in that it consists of a different nucleotide sequence. Each type of cells, tissues, fluids and medium recited in claim 3 or each type of agents, peptides, antibodies, compounds, blockers, acids, iron chelators and molecules recited in claims 4 and 6-8 has a different biological activity in that it has different cellular components and and effect. Thus, the different types of cells, tissues, fluids and medium recited in claim 3, different agents, peptides, antibodies, compounds, blockers, acids, iron chelators and molecules recited in claims 4 and 6-8 do not share a single structural similarity or biological activity, and do not have a common use that flows from the substantial structural feature.
Note that when the Markush grouping is for alternatives of chemical compounds, the alternatives are regarded as being of a similar nature where the following criteria are fulfilled:
(A) all alternatives have a common property or activity; AND
(B)(1) a common structure is present, that is, a significant structural element is shared by all of the alternatives; OR
(B)(2) in cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
The phrase “significant structural element is shared by all of the alternatives” refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity.
The phrase “recognized class of chemical compounds” means that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention, i.e. each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
There is no evidence of record to establish that different types of cells, tissues, fluids and medium recited in claim 3, or different agents, peptides, antibodies, compounds, blockers, acids, iron chelators and molecules recited in claims 4 and 6-8 possess the common property of a “single structural similarity” and a common use.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
9. 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 7 is 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 pre-AIA the applicant regards as the invention.
Regarding claim 7, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
10. 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.
Claim Rejections - 35 USC § 102
11. 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 1-5 and 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Toledano Furman et al. (Nano Lett. 2013; 7:3248-3255, as in IDS).
Claims 1, 4-5 and 9-11 are drawn to an artificial bioxome particle comprising a cell membrane component and designed to undergo fusion with a target cell, wherein the membrane component is derived from a pre-defined cellular or extracellular source and obtained by lipid extraction with a mild solvent system; and, wherein the bioxome particle is engineered to carry a cargo comprising at least one predetermined active molecule; and wherein the cargo can be released into the target cell after the fusion of the bioxome particle with the target cell. Dependent claims are directed to wherein the cargo comprises a plurality of active molecules (claim 2), different sources including mesenchymal stem cells (elected) (claim 3), different active molecules including organic molecule (elected) (claim 4), wherein the active molecule has a therapeutic effect (claim 5), the claimed bioxome particle is a long circulating, a slow release bioxome, a selective targeting bioxome, an immunogenic bioxome or any combination thereof (claim 9), a composition comprising the claimed bioxome particle and at least one carrier (claim 10), wherein the composition is a pharmaceutical composition and the carrier is the pharmaceutically acceptable carrier; wherein the composition is a cosmeceutical composition and the carrier is a cosmeceutically acceptable carrier or wherein the composition is an edible composition and the carrier is food grade carrier (claim 11).
The term "bioxome", which has no well-recognized meaning, is defined on p.8 of the specification as "an artificial, submicron nano-particle having resemblance to natural
Extracellular vesicles (EV). The particle size of the bioxome of the invention ranges from
0.03um to 5um". Therefore, any non-natural occruing EV with the size range of 0.03-5um is considered as "bioxome".
Toledano Furman et al. discloses nanoghosts (NGs) that are reconstructed from the whole cell membrane of mesenchymalstemcells(MSCs).The MSC-NGs are manufactured in a reproducible process by isolating intact MSC cell membranes (ghostcells), and homogenizing them into nano sized vesicles (nanoghosts) while entrapping a therapeutic of choice (see p.3248, 1st col., 2nd paragraph). The NGs exhibited narrow size distributions with similar average diameters of ~180nm (0.18um) (Figure1d). NG-particles undergo membrane fusion with target prostate tumor cells (PC3) in vivo and in vitro (Figure 3a and supplementary FigureS3). The NGs encapsulate the biologic model drug sTRAIL (i.e. organic molecule), the soluble form of TNF-related apoptosis-inducing ligand is released from hMSC-NGs (Figure1g), which is equivalent to the claimed cargo of active molecule, and comprising a plurality of active molecules as in claim 2. Toledano Furman teaches that the anti-tumor therapeutic effect of the MSC-NG including increased apoptos is with reduced proliferation and blood supply to the tumor (see p.3254,1st col., 2nd paragraph, Figures5a-Sc and 6a). Thus, the MSC-NGs encapsulating TRAIL disclosed by Toledano Furman meets the limitation recited in claims 1-5.
Toledano Furman also teaches that MSC-NGs suspended in PBS buffer for intravenous (IV) or intraperitoneal (IP) administration, which is a pharmaceutical composition comprising an artificial bioxome and a pharmaceutically acceptable carrier as in claims 10-11 (see p. 3250, 1st col., figure 3a, supplemental data under "Bio-distribution and specific in vivo tumor targeting by NGs"). Toledano Furman teaches that a single dose of sTRAIL-containing human MSC-derived NGs (NG-TRAIL) was sufficient to induce significant inhibition of tumor growth compared to untreated mice (see p. 3251 under "Antitumor Efficacy of sTRAIL-Encapsulating NGs", Figures 5a,5b & supplementary Figure S5). Toledano Furman also teaches that PEGylation was implemented (using activated PEGS5000) to reduce possible NG opsonin dependent uptake and increase circulation time, which is a long circulating, a slow release bioxome as in claim 9 (see p.3253, 1st col., 2nd paragraph, supplementary Figure 2a). Toledano Furman teaches that MSC-NG is tumor-specific and not species specific, providing evidence for active targeting, which is a selective targeting bioxome as in claim 9. MSC-derived NGs were fused with on the surface of, and within the cytoplasm of target cells (see p.3253, 1st col, 3rd paragraph). The MSC-NGs encapsulating TRAIL disclosed by Toledano Furman meets the limitations recited in claims 1-5 and 9-11. Thus, claims 1-5 and 9-11 are anticipated by Toledano Furman et al.
Claim Rejections - 35 USC § 103
12. 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 2 and 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Toledano Furman et al. (Nano Lett. 2013; 7:3248-3255, as in IDS) in view of Zhang et al. (W02013052167, published Apr 11, 2013, as in IDS), Chen et al. (WO2010144740, published Dec 16, 2010, as in IDS), Almouzen et al. (Pharm Res, 2013; 30:1137-1146) and Rustin et al. (US6133322, issued Oct 17, 2000).
Toledano Furman is set forth above but fails to teach a plurality of active molecules that are different active molecules as in claim 2, an immunogenic bioxome as in claim 9, a redoxome, wherein the cargo comprises at least one redox active free-radicals scavenging compound, fenton reaction complex blockers, hydroxyl radical trap, iron chelator or a lipid radical trap as in claim 6, capable of blocking LPO chain reaction including lipid radical/peroxide trap, ascorbic acid, vitamin E, vitamin D (elected), retinoids, lipoic acid, sterols as in claim 7, different iron chelator including desferrixamine (DFX) (elected), EDTA as in claim 8.
Zhang et al. (W02013052167) discloses a nanoparticle comprises a) an inner core comprising a non-cellular material; and b) an outer surface comprising a cellular membrane derived from a cell or a membrane (abstract). The nanoparticle neoplasm specific immunogenic composition has a diameter of from10nm to10pm, further comprises another active ingredient, or a releasable cargo (paragraph [0026]). The nanoparticle comprises a releasable cargo that can be located in any place inside or on the surface of the nanoparticle. The releasable cargo comprises one or more therapeutic agents as in claim 2(see paragraphs [0092]-[0093]). Zhang teaches that the preparation of toxin nanosponge consist of substrate-supported RBC bilayer membranes and incorporated pore-forming toxins (PFTs) in size of approximately 85nm (0.085um) in diameter (see paragraphs [0054]; [00200], FIGs18A-18C). The RBC membrane vesicles, without the polymeric cores, underwent fusion with the cellular membrane (see paragraphs [00203], figure19D). Zhang discloses a cancer cell-coated nanoparticle-based immuno-therapeutic vaccine with encapsulated payloads. Zhang teaches therapeutic efficacy in vivo using a melanoma murine model and observing for a reduction in tumor size upon direct administration of the treatment (see example 3, paragraph [00194], Figure 17). Zhang teaches that lipid-polymer hybrid nanoparticles have shown a more sustained release profile compared to polymeric nanoparticles with similar size owing to the diffusional barrier provided by the lipid monolayer coating (see paragraph [00146]). Zhang teaches that the nanoparticleis administered to a target site of the subject in need, including, a target dermal site, blood or plasma, a target organ, a target tumor site, or target cells, and further provides a mechanism to trigger the release of a releasable cargo at the target site (see paragraph [00105]). Zhang teaches administering to the subject in need one or more other active ingredient, with or without a pharmaceutically acceptable carrier or excipient, via any suitable administration route, including butoral, nasal, inhalational, parental, intravenous, intraperitoneal, subcutaneous, intramuscular, intradermal, topical or rectal (see paragraph [00123]). The methods of Zhang can be used for treating or preventing a disease, disorder, or condition in a subject in need, including a disease of the skin (see paragraphs [00103], [00129])
Chen et al. (WO2010144740) discloses lipid particles for the in vivo delivery of nucleic acids (see p. 2nd para.). The lipid formulation complexed with an oligonucleotide can be used to modify (e. g., decrease) target gene expression in a tumor cell in vivo or in vitro and may be fully encapsulated in the lipid particle. The nucleic acid in a lipid-nucleic acid particle includes any form of nucleic acid such as oligonucleotides, ribozymes, microRNA, and triplex-forming oligonucleotides including RNAi, antisense oligonucleotides, antagomirs and aptamers (see p. 5, last paragraph to p. 6, 1st paragraph; p. 40, 2nd paragraph to p. 52, 1st paragraph). The lipid particles of the invention are programmable fusion lipids. The vesicles have a size range of from 30 to 150 nm (i.e.0.03 to 0.15um) (see p.110, 2nd paragraph). The lipid artificial particles disclosed by Chen are resemblance to natural extracellular vesicles because the lipid particles are defined as "that include liposomes wherein a liposome is a structure having lipid-containing membranes enclosing an aqueous interior (see p. 29, 2nd paragraph).
Chen discloses that the lipid particles and related pharmaceutical compositions may be used to deliver a therapeutic agent to a cell, in vitro or in vivo. The compositions of the invention can be adsorbed to almost any cell type, e.g. tumor cell lines and may include anti-tumor drug or anti-inflammatory agents (see p. 39, 2nd paragraph to p. 11, last paragraph; p. 114, last paragraph to p. 115, 3rd paragraph).
Chen discloses that lipidic suspension may include lipid-protective agents which protect lipids against free-radical and lipid-peroxidative damages on storage. Lipophilic free-radical quenchers, such as a-tocopherol and water-soluble iron-specific chelators, such as ferrioxamine, are suitable (see p. 128, 3rd paragraph). Chen discloses that topical formulations also include an antioxidant (e.g., a radical scavenger), wherein the antioxidant is a phenolic compound, for example, butylhydroxytoluene, resveratrol, coenzyme Q10, or other flavinoids, or a vitamin, for example, vitamin E or vitamin C, lipoic acid, uric acid, a carotene such as beta-carotene or retinol (vitamin A), glutathione, melatonin, selenium, and ubiquinol as in claims 6-8.
Almouzen et al. (Pharm Res, 2013; 30:1137-1146) teaches vitamin D as in claim 7 can be encapsulated in nanoparticles and formations for vitamin-D3 based chemotherapy (see abstract). Rustin et al. (US6133322) teaches EDTA, desferrioxamine as in claim 8 are iron chelators (see col.). Hence, the addition of cargo which comprises redox active free-radicals scavenging compound comes within the scope of the customary practice followed by persons skilled in the art, especially as the advantages thus achieved can readily be foreseen for therapeutic purposes.
A person of ordinary skill in the art would have recognized that selecting and applying the known lipid nanoparticles comprising a plurality of active molecules, the known immunogenic bioxome , the known redoxome, wherein the cargo comprises at least one redox active free-radicals scavenging compound, fenton reaction complex blockers, hydroxyl radical trap, iron chelator or a lipid radical trap including vitamin D and different iron chelator including desferrixamine (DFX) and EDTA, and the know technique disclosed by Zhang, Chen, Almouzen and Rustin to the Toledano Furman’s MSC-NGs would have yielded the predictable result of an artificial bioxome particle and resulted in an improved product.
Using lipid nanoparticles comprising a plurality of active molecules, the known immunogenic bioxome , the known redoxome, wherein the cargo comprises at least one redox active free-radicals scavenging compound, fenton reaction complex blockers, hydroxyl radical trap, iron chelator or a lipid radical trap including vitamin D and different iron chelator including desferrixamine (DFX) and EDTA in the Toledano Furman’s MSC-NGs would exapand application of the Toledano Furman’s MSC-NGs for drug delivery and therapeutic purposes, and would increase patient’s satisfaction with treatment.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the known lipid nanoparticles comprising a plurality of active molecules, the known immunogenic bioxome , the known redoxome, wherein the cargo comprises at least one redox active free-radicals scavenging compound, fenton reaction complex blockers, hydroxyl radical trap, iron chelator or a lipid radical trap including vitamin D and different iron chelator including desferrixamine (DFX) and EDTA, and the know technique disclosed by Zhang, Chen, Almouzen and Rustin to the Toledano Furman’s MSC-NGs and yield the predictable result of an artificial bioxome particle as recited in claim 1.
Conclusion
13. NO CLAIM IS ALLOWED.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached on Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
June 18, 2023
/CHANG-YU WANG/Primary Examiner, Art Unit 1649