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 .
Claim Status
Claims 1-39 are pending.
Claims 1-11, 15-16, 19, 22 and 28-39 are withdrawn.
Claims 12-14, 17-18, 20-21 and 23-27 are under examination.
Election/Restrictions
Applicant’s election of the following invention
Invention
Group II, claims 12-27 drawn to BioNVs produced by the method of claim 1 and a composition comprising a therapeutic agent packaged in a hypo-BioNV, wherein said therapeutic agent is chosen from the group consisting of DNA, plasmid DNA, RNA, protein, small molecule, and combinations thereof
in the reply filed on 22nd, December, 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)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-11, and 28-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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’s election of the following species
Species
A. Therapeutic Agent Type of pro-inflammatory interleukin (claim 14)
B. Ligand Type of CAR ligands (claims 17-18)
C. Interleukin Type of knocked-out or regulated interleukins (claim 21)
in the reply filed on 22nd, December, 2022 is acknowledged. Claims 12-14, 17-18, 20-21 and 23-27 encompass the elected species.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as a species election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 15-16, 19 and 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Objections to Abstract
The abstract of the disclosure is objected to because it recites sentence fragments and not complete sentences. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 27 is objected to because of the following informalities:
Claim 27 claim uses the abbreviation “RAAS”, which has not been spelled out upon first use. Although claims are allowed abbreviations, if an abbreviation is not spelled out upon first use in a claim, MPEP §2429 states that Applicant only use abbreviations that are specifically defined in "WIPO Standard ST.25 (2009)” or that are well known and would be clear to someone who had not read the invention description.
Appropriate correction is required.
Claim Interpretation
Because claim 12 is dependent on withdrawn claim 1, for the sake of compact prosecution claim 12 is interpreted as follows:
BioNVs produced by a method of generating allogenic biomimetic nanovesicles (BioNVs) from gene edited iPSCs including the steps of:
disrupting cell membranes of the gene edited iPSCs using a method chosen from the group
consisting of sonicating, adaptive focused acoustics technology, extrusion, serial extrusion,
rupturing by detergents or enzymes, electroporation, and combinations thereof; and
purifying the BioNVs by a method chosen from the group consisting of microfiltration, affinity
chromatography, size exclusion chromatography, gel purification, centrifugation, and
combinations thereof.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 12 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring product without significantly more.
Applicant is directed to the 2019 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on 1/07/2019, which is found at: https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf; and the October 2019 Update: Subject Matter Eligibility, which is found at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf.
Briefly summarized here, the new guidance cites a two part test: is the claimed invention directed to a statutory class of invention (Step 1), if so then is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, prong one), if so then is the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, prong two), if not then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
Step 1
In regard to step 1, the claims are directed to a biomimetic nanovesicle (BioNV), which is a product and is a statutory class of invention. Accordingly, the requirements of step 1 are met.
Step 2A Prong One
In regard to Step 2A prong one, as stated above, the claims are directed to a BioNV. Applicant is directed to the art of Goh et al. (Sci Rep. 2017 Oct 30;7(1):14322.; see IDS filed 20th, March, 2022; henceforth “Goh”).
Goh evidences naturally occurring exosomes which are 50–150 nm in size endogenous vesicles that function as intermediaries for cell-to-cell communication and are produced by almost all mammalian cells. (pg. 2 1st para.).
Regarding the BioNV, Goh evidences BioNVs (“Bioinspired Cell-Derived Nanovesicles” or “Cell Derived Nanovesicles (CDNs)”; Title and abstract) showed similarities in terms of physical characterization, protein and lipid analysis to exosomes (abstract). Goh evidences BioNVs (CDNs) mimic several exosomes’ features, resulting in reduced clearance rates and efficient cellular uptake due to the innate targeting ability of the preserved surface proteins (pg. 2 5th para.) and specifically the results of Goh confirmed that the BioNVs (CDNs) mimicked natural exosomes (pg. 6 1st para. and Figure 3).
Regarding instant claim 12, the claim is a product-by process claim which recites that the BioNV is “produced by the method of claim 1”
where the method of claim 1 is “A method of generating allogenic biomimetic nanovesicles (BioNVs) from gene edited iPSCs including the steps of:
disrupting cell membranes of the gene edited iPSCs using a method chosen from the group
consisting of sonicating, adaptive focused acoustics technology, extrusion, serial extrusion,
rupturing by detergents or enzymes, electroporation, and combinations thereof; and
purifying the BioNVs by a method chosen from the group consisting of microfiltration, affinity
chromatography, size exclusion chromatography, gel purification, centrifugation, and
combinations thereof.”
Regarding instant claim 12, Applicant is reminded that product-by process claims are not limited by the manipulation of the recited steps, only the structure implied by the steps. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113).
Regarding claim 12, the method of making the BioNV does not structurally distinguish it from the naturally occurring exosomes or impart markedly different characteristics. Specifically, although the method of making requires the BioNVs are made “gene edited iPSCs” this does not impart an additional structure because it encompasses all possible gene edits, including those which are unrelated to protein markers that would be imparted onto the made BioNVs. Furthermore, Goh evidences BioNVs (CDNs) which are made by disrupting cell membrane by serial extrusion followed by purification (Figure 1; pg. 3rd para. “Cell Derived Nanovesicles (CDNs) and Exosomes production”) which are structurally indistinguishable and do not have markedly different characteristics from naturally occurring exosomes as discussed above.
Therefore, regarding Step 2A prong one, because Goh evidences BioNVs mimic naturally occurring exosomes, and then method of making the BioNVs as claimed does not impart a structural distinction from the naturally occurring exosomes, they are not considered to have markedly different characteristics from their naturally occurring counterparts (exosomes)(see MPEP 2106.04(c) for Markedly Different Characteristics Analysis).
Step 2A Prong Two
Regarding Step 2A prong two, the judicial exception is not integrated into a practical application.
Specifically, claim 12 recites the following additional elements:
“produced by the method of claim 1”
How the vesicles is made does not integrate the judicial exception into a practical application.
Step 2B
In regard to Step 2B, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
As stated above, instant claims are directed entirely to a structure of BioNV that is not markedly different than its naturally occurring exosome counterpart.
The only additional element that is recited is that the BioNV is “produced by the method of claim 1” which does not amount to sufficiently more because it does not impart an additional structure.
Two Part Test - Conclusion
Therefore, the claims are directed to a BioNV product that is not markedly different from its naturally occurring exosome counterpart, that is not integrated into a practical application, does not include elements that amount to significantly more than the judicial exception, and do not qualify as patent eligible subject matter under 35 U.S.C. § 101.
Claim Rejections - 35 USC § 112(b)
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.
Claims 12, 17-18 and 27 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 12 depends on a non-elected claim, and, therefore, is incomplete and indefinite.
Claim 17 recites “variable heavy chain lgG fragment (VHH nanobody or VNAR)” which includes parenthetical material. Claim 17 is therefore vague and indefinite in the use of parenthesis, since it is unclear whether the parenthetical material is or is not intended to be part of the claim.
Claim 17 recites “CORE Primary CAR” and “ADVANCE 2nd/3rd Gen CAR.” While the instant specification provides guidance on primary CAR and 2nd and 3rd generation CARs, the instant specification is silent to the term “CORE” or “ADVANCE,” and the art also appears to be silent on the specific meanings of these terms in the context of CARs. Therefore, the scope of “CORE” or “ADVANCE” in the context of the claims cannot be ascertained from the specification or the art and the metes and bounds of the claims are unclear.
Claim 17 recites “2nd/3rd Gen CAR,” due to the presence of the “/” it is unclear whether the scope is intended to encompass 2nd/3rd Gen CARs in the alternative or whether both (a mix of 2nd/3rd Gen CARs) is required. Accordingly, because it cannot be ascertained what the scope encompasses of multiple embodiments, the metes and bounds of the claim are indefinite.
Claim 18 recites “density of CAR expression on said HypoBioNVs is controlled,” which appears to be relative terminology. A claim may be rendered indefinite when a limitation of the claim is defined by reference to an object and the relationship between the limitation and the object is not sufficiently defined. That is, where the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite. See, e.g., Ex parte Miyazaki, 89 USPQ2d 1207 (Bd. Pat. App. & Inter. 2008) (precedential) and Ex parte Brummer, 12 USPQ2d 1653 (Bd. Pat. App. & Inter. 1989). In the instant case the density of CAR expression is dependent on some baseline or standard which is not sufficiently defined (see MPEP 2173.05(b)).
Claim 27 recites “gp120/gp41” part of a list of alternatives. Due to the presence of a “/” it is unclear whether both gp120 and gp41 are required or whether they are alternative options.
Claim Rejections - 35 USC § 112
Improper Markush
Claims 17 and 20 are rejected on the basis that they contain 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 § 2117.
Regarding claim 17, The Markush grouping of “a scFV, viral epitope recognition receptor (VERR), variable heavy chain lgG fragment (VHH nanobody or VNAR), affilin, chimeric endocrine receptor (CER) and a combination thereof” is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use. The defined alternatives are structurally distinct with distinct functions and do not appear to share a single structural similarity (e.g. an affilin is structurally distinct from an IgG fragment).
Regarding claim 20, the Markush grouping of “CORE Primary CAR, perforin, granzyme B, Fas Ligand and ADVANCE 2nd/3rd generation CAR” 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 defined alternatives are structurally distinct with distinct functions and do not appear to share a single structural similarity. Specifically, “perforin, granzyme B, Fas Ligand” are proteins with no common functions/uses and no structural similarities with each other or with ““CORE Primary CAR or ADVANCE 2nd/3rd generation CAR” which are chimeric antigen receptors.
Furthermore, regarding claims 17 and 20, the claims recites what appears to be a list of alternatives as “comprises one or more of,” which in not proper Markush language. Applicant is directed to MPEP 2117 which states claim language defined by a Markush grouping requires selection from a closed group "consisting of" the alternative members. Id. at 1280, 67 USPQ2d at 1196.
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 § 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.
Claim 12 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al. (Int J Mol Sci. 2020 Jan 5;21(1):343.; henceforth “Lee”).
Regarding claim 12, Lee discloses a BioNV (Cell-Engineered Nanovesicles or CENVs; Title and abstract; Figures 1-2; pg. 13 2nd para. “Preparation of iPSC-Derived EV and CENV”).
Regarding claim 12, Lee discloses the BioNVs (CENVs) are produced by a method with the steps of:
disrupting cell membranes of iPSCs using serial extrusion (Figure 1; pg. 13 2nd para. “Preparation of iPSC-Derived EV and CENV”); and
purifying the BioNVs by centrifugation (pg. 13 2nd para. “Preparation of iPSC-Derived EV and CENV”).
Regarding claim 12, the claim is a product-by process claim. Applicant is reminded that product-by process claims are not limited by the manipulation of the recited steps, only the structure implied by the steps. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113). In the instant case, the CENVs of Lee meet all the structural limitations of claim 12.
Regarding claim 12, the CENVs are structurally indistinct from allogenic nanovesicles because they are made from human iPSCS (pg. 13 2nd para. “Preparation of iPSC-Derived EV and CENV”). Additionally, the fact the biomimetic nanovesicles of instant claims are made from “gene-edited” cells also does not create a structural distinction because this includes all possible gene edits including those which would not structurally affect the cell membrane, which is what makes the nanovesicle.
Accordingly, Lee anticipates instant claims.
Claim 12 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fu et al. (Nat Commun. 2019 Sep 25;10(1):4355.; see IDS filed 20th, March, 2025; henceforth “Fu”).
Regarding claim 12, Fu discloses biomimetic nanovesicles (“exosomes as biomimetic nanovesicles”; abstract; see also pg. 10 col. 1 3rd-4th para. “Isolation and purification of exosomes”).
Regarding claim 12, the claim is a product-by process claim. Applicant is reminded that product-by process claims are not limited by the manipulation of the recited steps, only the structure implied by the steps. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113).
In the instant case, regarding claim 12 the exosomes as biomimetic nanovesicles meet all the structural limitations of claim 12 because they are biomimetic nanovesicles which are purified. They are allogeneic because they are from human cells and are therefore allogeneic to other human cells.
Additionally, regarding claim 12, the fact the biomimetic nanovesicles of instant claims are made from “gene-edited” cells also does not create a structural distinction because this includes all possible gene edits including those which would not structurally affect the cell membrane, which is what makes the nanovesicle.
Accordingly, Fu anticipates instant claims.
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, 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.
Claims 13, 17-18 and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Fu et al. (Nat Commun. 2019 Sep 25;10(1):4355.; see IDS filed 20th, March, 2025; henceforth “Fu”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”).
Regarding claim 13, Fu discloses a composition comprising a therapeutic agent (cytotoxic molecules; abstract and “lethal chemical compounds in the exosomes, including granzymes, lysosomal enzymes and perforin” pg. 2 2nd para.) in a biomimetic nanovesicle (abstract “exosomes as biomimetic nanovesicles”), wherein the nanovesicle expresses a chimeric antigen receptor (CAR) (“exosomes that carry CAR on their surface” abstract; see also Title; abstract; pg. 2 col. 2 3rd para.; pg. 3 col. 1 2nd para.; Figure 2) wherein the biomimetic nanovesicle comprises the CAR and does not comprise PD-1 (“CAR exosomes do not express Programmed cell Death protein 1 (PD1)”; abstract), and wherein the therapeutic agent is a protein (“granzymes, lysosomal enzymes and perforin” pg. 2 2nd para.).
However, regarding claim 13, Fu does not disclose the exosome comprise CD47 and do not comprise HLA 1/2.
Nevertheless, regarding claim 13, Deuse teaches human iPSCs lose their immunogenicity when major histocompatibility complex (MHC) class I and II genes are inactivated and CD47 is over-expressed (pg. 252 col. 1 1st para.; see also pg. 253 col. 2 last para. and pg. 254 col. 1 1st para). Deuse teaches somatic cells derived from these iPSCs are hypoimmunogenic and reliably evade immune rejection in fully MHC-mismatched allogeneic recipients and survive long-term without the use of immunosuppression (abstract; pg. 252 col. 1 1st para.).
Therefore, regarding claim 13, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles of Fu, and combine the known prior art element of the inactivation of the MHC class I and II genes and overexpression of CD47 of Deuse with the CAR-T cell of Fu to obtain the predictable result of a gene-edited CAR-T cell. One of ordinary skill would have been motivated to do so as taught by Deuse to make the nanovesicles hypoimmunogenic so that they can reliably evade immune rejection in fully MHC-mismatched allogeneic recipients and survive long-term without the use of immunosuppression (abstract; pg. 252 col. 1 1st para.). Regarding the reasonable expectation of success, Deuse evidences preparation of hypoimmunogenic gene-edited iPSCs which are B2M -/-, CIITA -/-, and CD47 +/+ (“B2M−/−CIITA−/− CD47 tg hiPSC colonies” pg. 253 col. 2 last para. and pg. 254 col. 1 1st para.) and therefore one of ordinary skill would have had a reasonable expectation of success in preparing CAR-T cells with these gene edits for producing exosomes/biomimetic nanovesicles.
Regarding claim 13, the nanovesicles suggested by Fu in view of Deuse would not express MHC class I and II genes and overexpresses CD47 and therefore would be hypoimmunogenic.
Regarding claim 13, the claim is a product-by process claim. Product-by process claims are not limited by the manipulation of the recited steps, only the structure implied by the steps. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113). In the instant case, the exosomes suggested by Fu in view of Deuse meet the structural requirements of instant claims because they comprise CD47 and a CAR, do not comprise HLA 1/2 or PD-1, and include therapeutic agents.
Regarding claim 17, further to the discussion of claim 13 above, Fu discloses the biomimetic nanovesicle comprises a surface coated with the CAR (“exosomes that carry CAR on their surface” abstract; see also Title; abstract; pg. 2 col. 2 3rd para.; pg. 3 col. 1 2nd para.; Figure 2), wherein the car comprises a scFV (“D5-5 scFv derived from trastuzumab” pg. 9 col. 2 1st para.; see also pg. 2 col. 1 1st para. and col. 2 2nd, 4th and 5th para.; Figure 1).
Regarding claim 18, further to the discussion of claim 13 above, Fu discloses the density of CAR expression on the biomimetic nanovesicles is comparable to the expression level of CARs in CAR-T cells (pg. 3 col. 2 2nd para.) and therefore the density is structurally equivalent to a controlled density similar to CAR-T expression of CARs.
Regarding claim 20, further to the discussion of claim 13, above, Fu discloses the biomimetic nanovesicle comprise perforin and granzyme B (“perforin and granzyme B molecules were notably expressed on both CAR-EXO-CTX and CAR-EXO-TTZ” pg. 4 col. 2 1st para.; see also Figure 2).
Regarding claim 21, further to the discussion of claim 13 above, Fu is silent to interleukins in the biomimetic nanovesicles and therefore it would have been obvious to a person of ordinary skill that the nanovesicles lack interleukins.
Hence, the claimed invention as a whole was prima facie obvious.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Fu et al. (Nat Commun. 2019 Sep 25;10(1):4355.; see IDS filed 20th, March, 2025; henceforth “Fu”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”) as applied to claim 13 above, and in further view of Agliardi et al. (Nat Commun. 2021 Jan 19;12(1):444; henceforth “Agliardi”) and Guo et al. (WO-2017176894-A1; henceforth “Guo”).
The teachings of Fu an Deuse above are hereby incorporated in their entirety.
Regarding claim 14, further to the discussion of claim 13 above, Fu and Deuse are silent to the nanovesicle with a pro-inflammatory interleukin.
Nevertheless, regarding claim 14, Guo teaches loading a nanovesicle (exosome) with a therapeutic agent which may be an interleukin (pg. 34; see also “exosomes are loaded with a therapeutic or diagnostic agent” pg. 27 1st para.).
Nevertheless, regarding claim 14, Agliardi teaches combining pro-inflammatory interleukin IL-12 with CAR-T therapy which results in a synergistic effect of promoting an effective and persistent anti-tumor response, even in the context of a poorly immunogenic model (pg. 3 col. 1). Agliardi teaches combing the IL-12 improves survival, has a strong effect in tumor control, does not result in significant systemic immune-activating effects (pg. 7 col. 1), and skew the myeloid compartment towards a proinflammatory phenotype (pg. 7 col. 2 last para.). Agliardi teaches the potential of IL-12 to support anti-tumor immunity has long been recognized (pg. 8 col. 2).
Therefore, regarding claim 14, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicle as suggested by Fu in view of Deuse, and combine the known prior art element of the IL-12 of Agliardi by loading it into the nanovesicle to obtain the predictable result of a nanovesicle comprising a protein. One of ordinary skill would have been motivated to do so as taught by Agliardi to provide a synergistic effect of promoting an effective and persistent anti-tumor response (pg. 3 col. 1). Regarding the reasonable expectation of success, Guo evidences loading exosomes with a therapeutic agent (pg. 1 line 35; pg. 5 line 14; pg. 6 line 11, pg. 8 lines 10 and 16; pg. 13 line 18; pg. 27 line 2; pg. 31 line 20; pg. 49 2nd and 3rd para.; pg. 50 last para.; pg. 51 line 19; pg. 52 line 32; pg. 55 2nd -4th para.; pg. 62 1st para.; pg. 66 2nd and last para.; pg. 67 2nd para.; pg. 68 line 1).
Hence, the claimed invention as a whole was prima facie obvious.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Fu et al. (Nat Commun. 2019 Sep 25;10(1):4355.; see IDS filed 20th, March, 2025; henceforth “Fu”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”) as applied to claim 13 above, and in further view of Guo et al. (Cancer Sci. 2021 Apr;112(4):1357-1368. Epub 2021 Feb 21.; henceforth “Guo2”).
The teachings of Fu an Deuse above are hereby incorporated in their entirety.
Regarding claim 23, further to the discussion of claim 13 above, although Fu teaches the nanovesicles comprise a CAR, Fu and Deuse are silent to a bispecific CAR.
Nevertheless, regarding claim 23, Guo2 teaches bispecific CARs (dual-target; abstract; see also Mixed, Bicistronic and Tandem; Figure 1) B-cell malignancies (pg. 1358 col. 1 1st para.). Guo teaches CAR T cells that that recognize multiple antigens ensure that tumor cells carrying either antigen can be specifically targeted and is a preventative strategy for antigen escape (pg. 1358 col. 1 2nd para.).
Therefore, regarding claim 23, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles as suggested by Fu in view of Deuse, and simply substitute the CAR-T cells of Fu for the bispecific CAR-T cells of Guo2 to obtain the predictable result of exosomes comprising a bispecific CAR. One of ordinary skill would have been motivated to do so as taught by Guo to target B-cell malignancies while preventing antigen escape (pg. 1358 col. 1 2nd para.). Regarding the reasonable expectation of success, Fu evidences preparation of nanovesicles from CAR-T cells (pg. 10 col. 1 3rd-4th para. “Isolation and purification of exosomes”).
Hence, the claimed invention as a whole was prima facie obvious.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Fu et al. (Nat Commun. 2019 Sep 25;10(1):4355.; see IDS filed 20th, March, 2025; henceforth “Fu”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”) as applied to claim 13 above, and in further view of Samanta et al. (Acta Pharmacol Sin. 2018 Apr;39(4):501-513. Epub 2017 Dec 7.; henceforth “Samanta”).
The teachings of Fu an Deuse above are hereby incorporated in their entirety.
Regarding claim 24, further to the discussion of claim 13 above, Fu and Deuse are silent to whether the nanovesicle comprises a fusion peptide embedded in a membrane.
Nevertheless, regarding claim 24, Samanta teaches and evidences that all exosomes comprise fusion peptides (“due to their endosomal origin, all exosomes contain membrane transport and fusion proteins” pg. 503 col. 2 2nd para.).
Therefore, regarding claim 24, it would have been obvious that the suggested nanovesicles, which are exosomes, would comprise a fusion peptide embedded in a membrane.
Hence, the claimed invention as a whole was prima facie obvious.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Fu et al. (Nat Commun. 2019 Sep 25;10(1):4355.; see IDS filed 20th, March, 2025; henceforth “Fu”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”) as applied to claim 13 above, and in further view of Alvarez-Erviti et al. (Nat Biotechnol. 2011 Apr;29(4):341-5. Epub 2011 Mar 20.; henceforth “Alvarez-Erviti”).
The teachings of Fu an Deuse above are hereby incorporated in their entirety.
Regarding claim 25, further to the discussion of claim 13 above, Fu and Deuse are silent to including a RVG peptide in the nanovesicle.
Nevertheless, regarding claim 25, Alvarez-Erviti teach including an RVG peptide in a nanovesicle (exosome) (abstract; pg. 341 col. 2 2nd-4th para.; Figures 1-3; pg. 342) to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.).
Therefore, regarding claim 25, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles as suggested by Fu in view of Deuse, and combine the known prior art element of the RVG peptide of Alvarez-Erviti to obtain the predicable result of a nanovesicle with a targeting peptide. One of ordinary skill would have been motivated to do so as taught by Alvarez-Erviti to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.). Regarding the reasonable expectation of success, Alvarez-Erviti evidences adding RVG peptides to exosomes (abstract).
Hence, the claimed invention as a whole was prima facie obvious.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Fu et al. (Nat Commun. 2019 Sep 25;10(1):4355.; see IDS filed 20th, March, 2025; henceforth “Fu”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”) as applied to claim 13 above, and in further view of Nakase et al. (Sci Rep. 2017 May 16;7(1):1991.; henceforth “Nakase”).
The teachings of Fu an Deuse above are hereby incorporated in their entirety.
Regarding claim 26, further to the discussion of claim 13 above, Fu and Deuse are silent to including a cell-penetrating peptide in the nanovesicle.
Nevertheless, regarding claim 26, Nakase teaches including cell-penetrating peptides on nanovesicles (extracellular vesicles or EVs) EVs to induce active macropinocytosis for effective cellular EV uptake (abstract; Figure 1) and to enhance cellular EV uptake (pg. 5 3rd para.).
Therefore, regarding claim 26, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles as suggested by Fu in view of Deuse, and combine the known prior art element of the cell-penetrating peptide of Nakase to obtain the predictable result of a nanovesicle with a cell-penetrating peptide. One of ordinary skill would have been motivated to do so as taught by Nakase to induce active macropinocytosis for effective cellular EV uptake (abstract; Figure 1) and to enhance cellular EV uptake (pg. 5 3rd para.). Regarding the reasonable expectation of success, Nakase evidences combining a cell penetrating peptide with a nanovesicle (Methods pg. 7-8).
Hence, the claimed invention as a whole was prima facie obvious.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Fu et al. (Nat Commun. 2019 Sep 25;10(1):4355.; see IDS filed 20th, March, 2025; henceforth “Fu”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”) as applied to claim 13 above, in view of Nakase et al. (Sci Rep. 2017 May 16;7(1):1991.; henceforth “Nakase”) as applied to claim 26 above, and in further view of Arakelyan et al. (Sci Rep. 2017 May 10;7(1):1695.; henceforth “Arakelyan”).
Regarding claim 27, further to the discussion of claims 13 and 26 above, although Nakase suggests including a cell-penetrating peptide, Fu, Deuse and Nakase are silent to including gp120 as a cell penetrating peptide.
Nevertheless, regarding claim 27, Arakelyan teaches the peptide gp120 which is a cell-penetrating peptide that mediates attachment and fusion to target cells (abstract; see also pg. 5 2nd para.).
Therefore, regarding claim 27, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicle as suggested by Fu in view of Deuse and Arakelyan, and combine the known prior art element of the gp120 fusion peptide of Arakelyan to obtain the predictable result of a nanovesicle with a fusion peptide. One of ordinary skill would have been motivated to do so as taught by Arakelyan to mediate attachment and fusion to target cells (abstract; see also pg. 5 2nd para.). Regarding the reasonable expectation of success, Nakase evidences combining a cell penetrating peptide with a nanovesicle (Methods pg. 7-8).
Hence, the claimed invention as a whole was prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Non- Statutory Double Patenting
U.S. Patent No. 12357704
Claim 12 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of US patent No. 12357704 (henceforth “Malcolm”).
The subject matter claimed in the instant application is disclosed in the referenced patent as
follows: the hypo-BioNV anticipates the hypo-BioNV of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 12, Malcolm claims a hypoimmunogenic induced pluripotent stem cell (iPSC)-derived biomimetic nanovesicle (claim 1). As set forth above, claim 12 is a product-by process claim. The hypoimmunogenic induced pluripotent stem cell (iPSC)-derived biomimetic nanovesicle of Malcom is structurally indistinguishable from the nanovesicle of instant claims.
Since the instant application claims are anticipated by cited patent claim, said claim is not patentably distinct.
Claims 13, 17-18, 20-21 and 24 and 26-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-11 and 14 of US patent No. 12357704 (henceforth “Malcolm”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”).
The subject matter claimed in the instant application is disclosed in the referenced patent as
follows: the hypo-BioNV makes obvious the hypo-BioNV of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 13, Malcolm claims a hypoimmunogenic induced pluripotent stem cell (iPSC)-derived biomimetic nanovesicle that is generated from an iPSC, comprises a CAR and does not comprise CD47, HLA 1/2 and PD-1 (claim 1). Malcolm claims the nanovesicle is capable of comprising a therapeutic agent is a small molecule, biologic, nucleic acid, and/or gene editing therapeutic (claim 1), and Malcolm claims specific therapeutic agents (claims 3 and 5-8).
However, regarding claim 13, Malcolm does not claim the nanovesicle comprises CD47.
Nevertheless, regarding claim 13, Deuse teaches human iPSCs lose their immunogenicity when major histocompatibility complex (MHC) class I and II genes are inactivated and CD47 is over-expressed (pg. 252 col. 1 1st para.; see also pg. 253 col. 2 last para. and pg. 254 col. 1 1st para). Deuse teaches somatic cells derived from these iPSCs are hypoimmunogenic and reliably evade immune rejection in fully MHC-mismatched allogeneic recipients and survive long-term without the use of immunosuppression (abstract; pg. 252 col. 1 1st para.).
Therefore, regarding claim 13, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles as claimed by Malcolm, and combine the known prior art element of overexpression of CD47 of Deuse with the iPSC of Malcolm to the predictable result of a gene-edited iPSC. One of ordinary skill would have been motivated to do so as taught by Deuse so that nanovesicles made can reliably evade immune rejection in fully MHC-mismatched allogeneic recipients and survive long-term without the use of immunosuppression (abstract; pg. 252 col. 1 1st para.). Regarding the reasonable expectation of success, Deuse evidences preparation of hypoimmunogenic gene-edited iPSCs which are B2M -/-, CIITA -/-, and CD47 +/+ (“B2M−/−CIITA−/− CD47 tg hiPSC colonies” pg. 253 col. 2 last para. and pg. 254 col. 1 1st para.).
As set forth above, claim 13 is a product-by process claim. The hypoimmunogenic induced pluripotent stem cell (iPSC)-derived biomimetic nanovesicle as claimed by Malcom in view of Deuse is structurally indistinguishable from the nanovesicle of instant claims.
Regarding claim 17, further to the discussion of claim 13 above, Malcolm claims the nanovesicle comprises a surface coated with the CAR, where the CAR comprises an scFV (claim 1).
Regarding claim 18, further to the discussion of claim 13 above, Malcolm claims the nanovesicle comprises a surface coated with the CAR (claim 1), and this expression amount is structurally indistinguishable from an amount that is controlled.
Regarding claim 20, further to the discussion of claim 13 above, Malcolm claims the nanovesicle comprises perforin (claim 14) or Fas ligand (claim 2).
Regarding claim 21, further to the discussion of claim 13 above, Malcolm does nor claim the presence of interleukins on the nanovesicle and therefore it would be obvious for one of ordinary skill to prepare the nanovesicle without interleukins.
Regarding claim 24, further to the discussion of claim 13 above, Malcolm claims the nanovesicle comprises a fusion peptide (vp1, vp2, or vp3 of SVV; claim 9).
Regarding claims 26-27, further to the discussion of claim 13, above, Malcom claims the nanovesicle comprises gp120 (instant claim 27), which is a cell-penetrating peptide (instant claim 26) (claim 10).
Since the instant application claims are obvious over cited patent claim, said claim is not patentably distinct.
Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-11 and 14 of US patent No. 12357704 (henceforth “Malcolm”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”) as applied to claim 1 above, and in further view of and in further view of Agliardi et al. (Nat Commun. 2021 Jan 19;12(1):444; henceforth “Agliardi”) and Guo et al. (WO-2017176894-A1; henceforth “Guo”).
The teachings of Malcolm and Deuse above are hereby incorporated in their entirety.
Regarding claim 14, further to the discussion of claim 13 above, Malcolm does not claim and Deuse is silent to the nanovesicle with a pro-inflammatory interleukin.
Nevertheless, regarding claim 14, Guo teaches loading a nanovesicle (exosome) with a therapeutic agent which may be an interleukin (pg. 34; see also “exosomes are loaded with a therapeutic or diagnostic agent” pg. 27 1st para.).
Nevertheless, regarding claim 14, Agliardi teaches combining pro-inflammatory interleukin IL-12 with CAR-T therapy which results in a synergistic effect of promoting an effective and persistent anti-tumor response, even in the context of a poorly immunogenic model (pg. 3 col. 1). Agliardi teaches combing the IL-12 improves survival, has a strong effect in tumor control, does not result in significant systemic immune-activating effects (pg. 7 col. 1), and skew the myeloid compartment towards a proinflammatory phenotype (pg. 7 col. 2 last para.). Agliardi teaches the potential of IL-12 to support anti-tumor immunity has long been recognized (pg. 8 col. 2).
Therefore, regarding claim 14, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicle as claimed by Malcolm in view of Deuse, and combine the known prior art element of the IL-12 of Agliardi by loading it into the nanovesicle to obtain the predictable result of a nanovesicle comprising a protein. One of ordinary skill would have been motivated to do so as taught by Agliardi to provide a synergistic effect of promoting an effective and persistent anti-tumor response (pg. 3 col. 1). Regarding the reasonable expectation of success, Guo evidences loading exosomes with a therapeutic agent (pg. 1 line 35; pg. 5 line 14; pg. 6 line 11, pg. 8 lines 10 and 16; pg. 13 line 18; pg. 27 line 2; pg. 31 line 20; pg. 49 2nd and 3rd para.; pg. 50 last para.; pg. 51 line 19; pg. 52 line 32; pg. 55 2nd -4th para.; pg. 62 1st para.; pg. 66 2nd and last para.; pg. 67 2nd para.; pg. 68 line 1).
Since the instant application claims are obvious over cited patent claim, said claim is not patentably distinct.
Claim 23 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-11 and 14 of US patent No. 12357704 (henceforth “Malcolm”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”) as applied to claim 1 above, and in further view of Guo et al. (Cancer Sci. 2021 Apr;112(4):1357-1368. Epub 2021 Feb 21.; henceforth “Guo2”).
The teachings of Malcolm and Deuse above are hereby incorporated in their entirety.
Regarding claim 23, further to the discussion of claim 13 above, Malcolm does not claim and Deuse is silent to a bispecific CAR.
Nevertheless, regarding claim 23, Guo2 teaches bispecific CARs (dual-target; abstract; see also Mixed, Bicistronic and Tandem; Figure 1) B-cell malignancies (pg. 1358 col. 1 1st para.). Guo teaches CAR T cells that that recognize multiple antigens ensure that tumor cells carrying either antigen can be specifically targeted and is a preventative strategy for antigen escape (pg. 1358 col. 1 2nd para.).
Therefore, regarding claim 23, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles as claimed by Malcolm in view of Deuse, and simply substitute the bispecific CAR of Guo2 for the CAR of Malcolm to obtain the predictable result of nanovesicles comprising a bispecific CAR. One of ordinary skill would have been motivated to do so as taught by Guo2 to target B-cell malignancies while preventing antigen escape (pg. 1358 col. 1 2nd para.).
Since the instant application claims are obvious over cited patent claim, said claim is not patentably distinct.
Claim 25 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-11 and 14 of US patent No. 12357704 (henceforth “Malcolm”) in view of Deuse et al. (Nat Biotechnol. 2019 Mar;37(3):252-258. Epub 2019 Feb 18.; see IDS filed 20th, March, 2025; henceforth “Deuse”) as applied to claim 1 above, and in further view of Alvarez-Erviti et al. (Nat Biotechnol. 2011 Apr;29(4):341-5. Epub 2011 Mar 20.; henceforth “Alvarez-Erviti”).
The teachings of Malcolm and Deuse above are hereby incorporated in their entirety.
Regarding claim 25, further to the discussion of claim 13 above, Malcolm does not claim and Deuse are silent to including a RVG peptide in the nanovesicle.
Nevertheless, regarding claim 25, Alvarez-Erviti teach including an RVG peptide in a nanovesicle (exosome) (abstract; pg. 341 col. 2 2nd-4th para.; Figures 1-3; pg. 342) to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.).
Therefore, regarding claim 25, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles claimed by Malcom in view of Deuse, and combine the known prior art element of the RVG peptide of Alvarez-Erviti to obtain the predicable result of a nanovesicle with a targeting peptide. One of ordinary skill would have been motivated to do so as taught by Alvarez-Erviti to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.). Regarding the reasonable expectation of success, Alvarez-Erviti evidences adding RVG peptides to exosomes (abstract).
Since the instant application claims are obvious over cited patent claim, said claim is not patentably distinct.
Provisional Non- Statutory Double Patenting
U.S. Co-pending App 18/879,371
Claim 12 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-112 of copending application No. 18/879,371 (claims filed 27th, December, 2024).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the biomimetic nanovesicle anticipates the biomimetic nanovesicle of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 12, U.S. Co-pending App ‘371 claims a biomimetic nanovesicle (claim 1), which is made from a modified iPSC (claim 5). As set forth above, claim 12 is a product-by process claim. The biomimetic nanovesicle of U.S. Co-pending App ‘371 is structurally indistinguishable from the nanovesicle of instant claims.
Since the instant application claim is anticipated by cited application claims, said claims are not patentably distinct.
Claims 13, 17-18, 20-21 and 24 and 26-27 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-112 of copending application No. 18/879,371 (claims filed 27th, December, 2024).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the biomimetic nanovesicle makes obvious the biomimetic nanovesicle of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 13, U.S. co-pending App ’371 claims a biomimetic nanovesicle (claim 1), which is made from a modified iPSC (claim 5) that comprises CD47 (claims 29, 31, and 45-47) and CAR (claims 48, 51-54) and does not comprise HLA 1/2 (claim 7) and PD-1 (claim 17), and is loaded with a therapeutic agent (gene editing payload; claim 1). It would be obvious to a person of ordinary skill to combine these separately claimed embodiments. As set forth above, claim 13 is a product-by process claim. The biomimetic nanovesicle as suggested by U.S. co-pending App ’371 is structurally indistinguishable from the nanovesicle of instant claims.
Regarding claim 17, further to the discussion of claim 13 above, U.S. co-pending App ’371 claims the nanovesicle comprises the CAR (claims 48, 51-54), and it would be obvious to a person of ordinary skill that that it would be expressed on the surface because this is where CARs are expressed. U.S. co-pending App ’371 claims the CAR comprises an scFV (claims 48 and 50).
Regarding claim 18, further to the discussion of claim 13 above, U.S. co-pending App ’371 claims the nanovesicle comprises the CAR (claims 48, 51-54), and it would be obvious to a person of ordinary skill that that it would be expressed on the surface because this is where CARs are expressed. This expression amount is structurally indistinguishable from an amount that is controlled. Regarding claim 20, further to the discussion of claim 13 above, U.S. co-pending App ’371 claims the nanovesicle comprises Fas Ligand (claim 36 and 45-46).
Regarding claim 21, further to the discussion of claim 13 above, U.S. co-pending App ’371 claims the nanovesicle lacks interleukins (claims 18-21).
Regarding claim 24, further to the discussion of claim 13 above, U.S. co-pending App ’371 claims the nanovesicle comprises a fusion peptide (claim 48).
Regarding claims 26-27, further to the discussion of claim 13, above, U.S. co-pending App ’371 claims the nanovesicle comprises gp120 (instant claim 27), which is a cell-penetrating peptide (instant claim 26) (claim 49).
Since the instant application claims are obvious over cited application claims, said claims are not patentably distinct.
Claim 14 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-112 of copending application No. 18/879,371 (claims filed 27th, December, 2024) as applied to claim 13 above, and in further view of Agliardi et al. (Nat Commun. 2021 Jan 19;12(1):444; henceforth “Agliardi”) and Guo et al. (WO-2017176894-A1; henceforth “Guo”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The teachings of U.S. co-pending App ’371 above are hereby incorporated in their entirety.
Regarding claim 14, further to the discussion of claim 13 above, U.S. co-pending App ’371 does not claim loading the nanovesicle with a pro-inflammatory interleukin.
Nevertheless, regarding claim 14, Guo teaches loading a nanovesicle (exosome) with a therapeutic agent which may be an interleukin (pg. 34; see also “exosomes are loaded with a therapeutic or diagnostic agent” pg. 27 1st para.).
Nevertheless, regarding claim 14, Agliardi teaches combining pro-inflammatory interleukin IL-12 with CAR-T therapy which results in a synergistic effect of promoting an effective and persistent anti-tumor response, even in the context of a poorly immunogenic model (pg. 3 col. 1). Agliardi teaches combing the IL-12 improves survival, has a strong effect in tumor control, does not result in significant systemic immune-activating effects (pg. 7 col. 1), and skew the myeloid compartment towards a proinflammatory phenotype (pg. 7 col. 2 last para.). Agliardi teaches the potential of IL-12 to support anti-tumor immunity has long been recognized (pg. 8 col. 2).
Therefore, regarding claim 14, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicle as claimed by U.S. co-pending App ’371 , and combine the known prior art element of the IL-12 of Agliardi by loading it into the nanovesicle to obtain the predictable result of a nanovesicle comprising a protein. One of ordinary skill would have been motivated to do so as taught by Agliardi to provide a synergistic effect of promoting an effective and persistent anti-tumor response (pg. 3 col. 1). Regarding the reasonable expectation of success, Guo evidences loading exosomes with a therapeutic agent (pg. 1 line 35; pg. 5 line 14; pg. 6 line 11, pg. 8 lines 10 and 16; pg. 13 line 18; pg. 27 line 2; pg. 31 line 20; pg. 49 2nd and 3rd para.; pg. 50 last para.; pg. 51 line 19; pg. 52 line 32; pg. 55 2nd -4th para.; pg. 62 1st para.; pg. 66 2nd and last para.; pg. 67 2nd para.; pg. 68 line 1).
Since the instant application claims are obvious over cited application claims, in view of Agliardi and Guo, said claims are not patentably distinct.
Claim 23 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-112 of copending application No. 18/879,371 (claims filed 27th, December, 2024) as applied to claim 13 above, and in further view of Guo et al. (Cancer Sci. 2021 Apr;112(4):1357-1368. Epub 2021 Feb 21.; henceforth “Guo2”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The teachings of U.S. co-pending App ’371 above are hereby incorporated in their entirety.
Regarding claim 23, further to the discussion of claim 13 above, U.S. co-pending App ’371 does not claim a bispecific CAR.
Nevertheless, regarding claim 23, Guo2 teaches bispecific CARs (dual-target; abstract; see also Mixed, Bicistronic and Tandem; Figure 1) B-cell malignancies (pg. 1358 col. 1 1st para.). Guo teaches CAR T cells that that recognize multiple antigens ensure that tumor cells carrying either antigen can be specifically targeted and is a preventative strategy for antigen escape (pg. 1358 col. 1 2nd para.).
Therefore, regarding claim 23, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles as claimed by U.S. co-pending App ’371, and simply substitute the bispecific CAR of Guo2 for the CAR of Malcolm to obtain the predictable result of nanovesicles comprising a bispecific CAR. One of ordinary skill would have been motivated to do so as taught by Guo2 to target B-cell malignancies while preventing antigen escape (pg. 1358 col. 1 2nd para.).
Since the instant application claims are obvious over cited application claims, in view of Agliardi and Guo2, said claims are not patentably distinct.
Claim 25 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-112 of copending application No. 18/879,371 (claims filed 27th, December, 2024) as applied to claim 13 above, and in further view of Alvarez-Erviti et al. (Nat Biotechnol. 2011 Apr;29(4):341-5. Epub 2011 Mar 20.; henceforth “Alvarez-Erviti”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The teachings of U.S. co-pending App ’371 above are hereby incorporated in their entirety.
Regarding claim 25, further to the discussion of claim 13 above, U.S. co-pending App ’371 does not claim including a RVG peptide in the nanovesicle.
Nevertheless, regarding claim 25, Alvarez-Erviti teach including an RVG peptide in a nanovesicle (exosome) (abstract; pg. 341 col. 2 2nd-4th para.; Figures 1-3; pg. 342) to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.).
Therefore, regarding claim 25, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles claimed by U.S. co-pending App ’371 , and combine the known prior art element of the RVG peptide of Alvarez-Erviti to obtain the predicable result of a nanovesicle with a targeting peptide. One of ordinary skill would have been motivated to do so as taught by Alvarez-Erviti to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.). Regarding the reasonable expectation of success, Alvarez-Erviti evidences adding RVG peptides to exosomes (abstract).
Since the instant application claims are obvious over cited application claims, in view of Alvarez-Erviti, said claims are not patentably distinct.
U.S. Co-pending Application No. 18/868,258
Claim 12 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 107-112 of copending application No. 18/868,258 (claims filed 22nd, November, 2024).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the biomimetic nanovesicle anticipates the biomimetic nanovesicle of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 12, U.S. Co-pending App ‘258 claims a biomimetic nanovesicle (claims 107 and 108). As set forth above, claim 12 is a product-by process claim. The biomimetic nanovesicle of U.S. Co-pending App ‘258 is structurally indistinguishable from the nanovesicle of instant claims.
Since the instant application claim is anticipated by cited application claims, said claims are not patentably distinct.
Claims 13, 17-18, 20-21, 24 and 26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50-51, 56-57, 73, and 107-112 of copending application No. 18/868,258 (claims filed 22nd, November, 2024).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the biomimetic nanovesicle makes obvious the biomimetic nanovesicle of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 13, U.S. co-pending App ’258 claims an allogeneic biomimetic nanovesicle (claims 107-112), that comprises CD47 (claim 108) and does not comprise HLA 1/2 (claim 107-108) and PD-1 (claim 107-108), and is loaded with a therapeutic agent (gene editing payload; claim 109). It would be obvious to a person of ordinary skill to combine these separately claimed embodiments. U.S. co-pending App ’258 separately claims methods of making biomimetic nanovesicles to comprise CARs (claims 50, 56-57 and 73) and therefore it would be obvious to a person of ordinary skill to combine a CAR with the claimed nanovesicle. As set forth above, claim 13 is a product-by process claim. The biomimetic nanovesicle as suggested by the claims of U.S. co-pending App ’ 258 is structurally indistinguishable from the nanovesicle of instant claims.
Regarding claim 17, further to the discussion of claim 13 above, U.S. co-pending App ’258 claims suggest the nanovesicle comprises the CAR and it would be obvious to a person of ordinary skill that that it would be expressed on the surface because this is where CARs are expressed. U.S. co-pending App ’371 claims the CAR comprises an scFV (claims 50, 56-57 and 73).
Regarding claim 18, further to the discussion of claim 13 above, .S. co-pending App ’258 claims suggest the nanovesicle comprises the CAR and it would be obvious to a person of ordinary skill that that it would be expressed on the surface because this is where CARs are expressed. This expression amount is structurally indistinguishable from an amount that is controlled. Regarding claim 20, further to the discussion of claim 13 above, U.S. co-pending App ’258 claims the nanovesicle comprises Fas Ligand (claims 107-108).
Regarding claim 21, further to the discussion of claim 13 above, U.S. co-pending App ’258 claims the nanovesicle lacks interleukins (claims 107-108).
Regarding claim 24, further to the discussion of claim 13 above, U.S. co-pending App ’258 claims the nanovesicle comprises a fusion peptide (claim 56)
Regarding claims 26-27, further to the discussion of claim 13, above, U.S. co-pending App ’258 claims the nanovesicle comprises gp120 (instant claim 27), which is a cell-penetrating peptide (instant claim 26) (claim 51).
Since the instant application claims are obvious over cited application claims, said claims are not patentably distinct.
Claim 14 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50-51, 56-57, 73, and 107-112 of copending application No. 18/868,258 (claims filed 22nd, November, 2024) applied to claim 13 above, and in further view of Agliardi et al. (Nat Commun. 2021 Jan 19;12(1):444; henceforth “Agliardi”) and Guo et al. (WO-2017176894-A1; henceforth “Guo”).
The teachings of U.S. co-pending App ’258 above are hereby incorporated in their entirety.
Regarding claim 14, further to the discussion of claim 13 above, U.S. co-pending App ’258 does not claim loading the nanovesicle with a pro-inflammatory interleukin.
Nevertheless, regarding claim 14, Guo teaches loading a nanovesicle (exosome) with a therapeutic agent which may be an interleukin (pg. 34; see also “exosomes are loaded with a therapeutic or diagnostic agent” pg. 27 1st para.).
Nevertheless, regarding claim 14, Agliardi teaches combining pro-inflammatory interleukin IL-12 with CAR-T therapy which results in a synergistic effect of promoting an effective and persistent anti-tumor response, even in the context of a poorly immunogenic model (pg. 3 col. 1). Agliardi teaches combing the IL-12 improves survival, has a strong effect in tumor control, does not result in significant systemic immune-activating effects (pg. 7 col. 1), and skew the myeloid compartment towards a proinflammatory phenotype (pg. 7 col. 2 last para.). Agliardi teaches the potential of IL-12 to support anti-tumor immunity has long been recognized (pg. 8 col. 2).
Therefore, regarding claim 14, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicle as claimed by U.S. co-pending App ’258 , and combine the known prior art element of the IL-12 of Agliardi by loading it into the nanovesicle to obtain the predictable result of a nanovesicle comprising a protein. One of ordinary skill would have been motivated to do so as taught by Agliardi to provide a synergistic effect of promoting an effective and persistent anti-tumor response (pg. 3 col. 1). Regarding the reasonable expectation of success, Guo evidences loading exosomes with a therapeutic agent (pg. 1 line 35; pg. 5 line 14; pg. 6 line 11, pg. 8 lines 10 and 16; pg. 13 line 18; pg. 27 line 2; pg. 31 line 20; pg. 49 2nd and 3rd para.; pg. 50 last para.; pg. 51 line 19; pg. 52 line 32; pg. 55 2nd -4th para.; pg. 62 1st para.; pg. 66 2nd and last para.; pg. 67 2nd para.; pg. 68 line 1).
Since the instant application claims are obvious over cited application claims, in view of Agliardi and Guo, said claims are not patentably distinct.
Claim 23 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50-51, 56-57, 73, and 107-112 of copending application No. 18/868,258 (claims filed 22nd, November, 2024) applied to claim 13 above, and in further view of Guo et al. (Cancer Sci. 2021 Apr;112(4):1357-1368. Epub 2021 Feb 21.; henceforth “Guo2”).
The teachings of U.S. co-pending App ’258 above are hereby incorporated in their entirety.
Regarding claim 23, further to the discussion of claim 13 above, U.S. co-pending App ’258 does not claim a bispecific CAR.
Nevertheless, regarding claim 23, Guo2 teaches bispecific CARs (dual-target; abstract; see also Mixed, Bicistronic and Tandem; Figure 1) B-cell malignancies (pg. 1358 col. 1 1st para.). Guo teaches CAR T cells that that recognize multiple antigens ensure that tumor cells carrying either antigen can be specifically targeted and is a preventative strategy for antigen escape (pg. 1358 col. 1 2nd para.).
Therefore, regarding claim 23, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles as claimed by U.S. co-pending App ’258, and simply substitute the bispecific CAR of Guo2 for the CAR of Malcolm to obtain the predictable result of nanovesicles comprising a bispecific CAR. One of ordinary skill would have been motivated to do so as taught by Guo2 to target B-cell malignancies while preventing antigen escape (pg. 1358 col. 1 2nd para.).
Since the instant application claims are obvious over cited application claims, in view of Agliardi and Guo2 , said claims are not patentably distinct.
Claim 25 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50-51, 56-57, 73, and 107-112 of copending application No. 18/868,258 (claims filed 22nd, November, 2024) applied to claim 13 above, and in further view of Alvarez-Erviti et al. (Nat Biotechnol. 2011 Apr;29(4):341-5. Epub 2011 Mar 20.; henceforth “Alvarez-Erviti”).
The teachings of U.S. co-pending App ’258 above are hereby incorporated in their entirety.
Regarding claim 25, further to the discussion of claim 13 above, U.S. co-pending App ’258 does not claim including a RVG peptide in the nanovesicle.
Nevertheless, regarding claim 25, Alvarez-Erviti teach including an RVG peptide in a nanovesicle (exosome) (abstract; pg. 341 col. 2 2nd-4th para.; Figures 1-3; pg. 342) to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.).
Therefore, regarding claim 25, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles claimed by U.S. co-pending App ’258, and combine the known prior art element of the RVG peptide of Alvarez-Erviti to obtain the predicable result of a nanovesicle with a targeting peptide. One of ordinary skill would have been motivated to do so as taught by Alvarez-Erviti to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.). Regarding the reasonable expectation of success, Alvarez-Erviti evidences adding RVG peptides to exosomes (abstract).
Since the instant application claims are obvious over cited application claims, in view of Alvarez-Erviti, said claims are not patentably distinct.
U.S. Co-pending Application No. 19/129,496
Claim 12 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-83 of copending application No. 19/129,496 (claims filed 13th, May, 2015)
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the biomimetic nanovesicle anticipates the biomimetic nanovesicle of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 12, U.S. Co-pending App ‘496 claims a biomimetic nanovesicle (claims 1-83). As set forth above, claim 12 is a product-by process claim. The biomimetic nanovesicle of U.S. Co-pending App ‘496 is structurally indistinguishable from the nanovesicle of instant claims.
Since the instant application claim is anticipated by cited application claims, said claims are not patentably distinct.
Claims 13, 17-18, 20-21, 24 and 26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-83 of copending application No. 19/129,496 (claims filed 13th, May, 2015).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the biomimetic nanovesicle makes obvious the biomimetic nanovesicle of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 13, U.S. co-pending App ’496 claims an allogeneic (claim 61) biomimetic nanovesicle (claims 1-82), that comprises CD47 (claims 49, 51, 53, 66-68), a CAR (claims 69, 72-75) and does not comprise HLA 1/2 (claim 32-36, 63-64) and PD-1 (claim 39, 64-65), and is loaded with a therapeutic agent (gene editing payload; claim 1). It would be obvious to a person of ordinary skill to combine these separately claimed embodiments. As set forth above, claim 13 is a product-by process claim. The biomimetic nanovesicle as suggested by the claims of U.S. co-pending App ‘496 is structurally indistinguishable from the nanovesicle of instant claims.
Regarding claim 17, further to the discussion of claim 13 above, U.S. co-pending App ’496 claims suggest the nanovesicle comprises the CAR and it would be obvious to a person of ordinary skill that that it would be expressed on the surface because this is where CARs are expressed. U.S. co-pending App ’496 claims the CAR comprises an scFV (claims 69, 71-72).
Regarding claim 18, further to the discussion of claim 13 above, U.S. co-pending App ’496 claims suggest the nanovesicle comprises the CAR and it would be obvious to a person of ordinary skill that that it would be expressed on the surface because this is where CARs are expressed. This expression amount is structurally indistinguishable from an amount that is controlled. Regarding claim 20, further to the discussion of claim 13 above, U.S. co-pending App ’496 claims the nanovesicle comprises Fas Ligand (claims 58 and 66-67).
Regarding claim 21, further to the discussion of claim 13 above, U.S. co-pending App ’496 claims the nanovesicle lacks interleukins (claims 40-43).
Regarding claim 24, further to the discussion of claim 13 above, U.S. co-pending App ’496 claims the nanovesicle comprises a fusion peptide (claims 19 and 69).
Regarding claims 26-27, further to the discussion of claim 13, above, U.S. co-pending App ’495 claims the nanovesicle comprises a VERR (claim 69), and U.S. co-pending App ’496 claims a method of making a nanovesicle with a VERR of gp120 and it would therefore be obvious to combine the gp120 (instant claim 27), which is a cell-penetrating peptide (instant claim 26) (claim 51).
Since the instant application claims are obvious over cited application claims, said claims are not patentably distinct.
Claim 14 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable claims 1-83 of copending application No. 19/129,496 (claims filed 13th, May, 2015) as applied to claim 13 above, and in further view of Agliardi et al. (Nat Commun. 2021 Jan 19;12(1):444; henceforth “Agliardi”) and Guo et al. (WO-2017176894-A1; henceforth “Guo”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The teachings of U.S. co-pending App ’496 above are hereby incorporated in their entirety.
Regarding claim 14, further to the discussion of claim 13 above, U.S. co-pending App ’496 does not claim loading the nanovesicle with a pro-inflammatory interleukin.
Nevertheless, regarding claim 14, Guo teaches loading a nanovesicle (exosome) with a therapeutic agent which may be an interleukin (pg. 34; see also “exosomes are loaded with a therapeutic or diagnostic agent” pg. 27 1st para.).
Nevertheless, regarding claim 14, Agliardi teaches combining pro-inflammatory interleukin IL-12 with CAR-T therapy which results in a synergistic effect of promoting an effective and persistent anti-tumor response, even in the context of a poorly immunogenic model (pg. 3 col. 1). Agliardi teaches combing the IL-12 improves survival, has a strong effect in tumor control, does not result in significant systemic immune-activating effects (pg. 7 col. 1), and skew the myeloid compartment towards a proinflammatory phenotype (pg. 7 col. 2 last para.). Agliardi teaches the potential of IL-12 to support anti-tumor immunity has long been recognized (pg. 8 col. 2).
Therefore, regarding claim 14, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicle as claimed by U.S. co-pending App ’496, and combine the known prior art element of the IL-12 of Agliardi by loading it into the nanovesicle to obtain the predictable result of a nanovesicle comprising a protein. One of ordinary skill would have been motivated to do so as taught by Agliardi to provide a synergistic effect of promoting an effective and persistent anti-tumor response (pg. 3 col. 1). Regarding the reasonable expectation of success, Guo evidences loading exosomes with a therapeutic agent (pg. 1 line 35; pg. 5 line 14; pg. 6 line 11, pg. 8 lines 10 and 16; pg. 13 line 18; pg. 27 line 2; pg. 31 line 20; pg. 49 2nd and 3rd para.; pg. 50 last para.; pg. 51 line 19; pg. 52 line 32; pg. 55 2nd -4th para.; pg. 62 1st para.; pg. 66 2nd and last para.; pg. 67 2nd para.; pg. 68 line 1).
Since the instant application claims are obvious over cited application claims, in view of Agliardi and Guo, said claims are not patentably distinct.
Claim 23 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-83 of copending application No. 19/129,496 (claims filed 13th, May, 2015) as applied to claim 13 above, and in further view of Guo et al. (Cancer Sci. 2021 Apr;112(4):1357-1368. Epub 2021 Feb 21.; henceforth “Guo2”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The teachings of U.S. co-pending App ’496 above are hereby incorporated in their entirety.
Regarding claim 23, further to the discussion of claim 13 above, U.S. co-pending App ’496 does not claim a bispecific CAR.
Nevertheless, regarding claim 23, Guo2 teaches bispecific CARs (dual-target; abstract; see also Mixed, Bicistronic and Tandem; Figure 1) B-cell malignancies (pg. 1358 col. 1 1st para.). Guo teaches CAR T cells that that recognize multiple antigens ensure that tumor cells carrying either antigen can be specifically targeted and is a preventative strategy for antigen escape (pg. 1358 col. 1 2nd para.).
Therefore, regarding claim 23, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles as claimed by U.S. co-pending App ’496, and simply substitute the bispecific CAR of Guo2 for the CAR of Malcolm to obtain the predictable result of nanovesicles comprising a bispecific CAR. One of ordinary skill would have been motivated to do so as taught by Guo2 to target B-cell malignancies while preventing antigen escape (pg. 1358 col. 1 2nd para.).
Since the instant application claims are obvious over cited application claims, in view of Agliardi and Guo2, said claims are not patentably distinct.
Claim 25 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-83 of copending application No. 19/129,496 (claims filed 13th, May, 2015) as applied to claim 13 above, and in further view of Alvarez-Erviti et al. (Nat Biotechnol. 2011 Apr;29(4):341-5. Epub 2011 Mar 20.; henceforth “Alvarez-Erviti”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The teachings of U.S. co-pending App ’496 above are hereby incorporated in their entirety.
Regarding claim 25, further to the discussion of claim 13 above, U.S. co-pending App ’496 does not claim including a RVG peptide in the nanovesicle.
Nevertheless, regarding claim 25, Alvarez-Erviti teach including an RVG peptide in a nanovesicle (exosome) (abstract; pg. 341 col. 2 2nd-4th para.; Figures 1-3; pg. 342) to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.).
Therefore, regarding claim 25, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicles claimed by U.S. co-pending App ’496, and combine the known prior art element of the RVG peptide of Alvarez-Erviti to obtain the predicable result of a nanovesicle with a targeting peptide. One of ordinary skill would have been motivated to do so as taught by Alvarez-Erviti to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.). Regarding the reasonable expectation of success, Alvarez-Erviti evidences adding RVG peptides to exosomes (abstract).
Since the instant application claims are obvious over cited application claims, in view of Alvarez-Erviti, said claims are not patentably distinct.
U.S. Co-pending Application No. 18/868,324
Claim 12 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116 to 118 of copending application No. 18/868,324 (claims filed 24th, November, 2025)
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the biomimetic nanovesicle anticipates the biomimetic nanovesicle of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 12, U.S. Co-pending App ‘324 claims an allogeneic biomimetic nanovesicle (claims 116-118). As set forth above, claim 12 is a product-by process claim. The biomimetic nanovesicle of U.S. Co-pending App ‘324 is structurally indistinguishable from the nanovesicle of instant claims.
Since the instant application claim is anticipated by cited application claims, said claims are not patentably distinct.
U.S. Copending Application No. 18/571,007
Claim 12 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-14, 16, 18-19 and 21-23 of copending application No. 18/571,007 (claims filed 7th, August, 2024)
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the biomimetic nanovesicle anticipates the biomimetic nanovesicle of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 12, U.S. Co-pending App ‘007 claims a composition comprising an exosome claims 13-14, 16, 18-19 and 21-23). As set forth above, claim 12 is a product-by process claim. The exosomes of U.S. Co-pending App ‘007 is structurally indistinguishable from the nanovesicle of instant claims.
Since the instant application claim is anticipated by cited application claims, said claims are not patentably distinct.
Claims 13-14, 17-18, 20-21 and 23-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-14, 16, 18-19 and 21-23 of copending application No. 18/571,007 (claims filed 7th, August, 2024) in view of Goh et al. (Sci Rep. 2017 Oct 30;7(1):14322.; see IDS filed 20th, March, 2022; henceforth “Goh”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the exosome makes obvious the biomimetic nanovesicle of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 13, U.S. co-pending App ’007 claims a composition comprising an exosome an (claims 13), that comprises a CAR (claims 16, 19 and 22) CD47 (claim 19) and does not comprise HLA 1/2 (claim 19) and PD-1 (claim 19), and is loaded with a therapeutic agent (claim 13). Because Go teaches biomimetic vesicles are structurally similar to exosomes (pg. 6 1st para. and Figure 3), the nanovesicles of the instant application are an obvious variant of the exosomes of U.S. co-pending App ’007.
Regarding claim 14, further to the discussion of claim 13 above, U.S. co-pending App ’007 claims the therapeutic agent is a proinflammatory interleukin (claim 14).
Regarding claim 17, further to the discussion of claim 13 above, U.S. co-pending App ’007 claims suggest the nanovesicle comprises the CAR and it would be obvious to a person of ordinary skill that that it would be expressed on the surface because this is where CARs are expressed. U.S. co-pending App ’371 claims the CAR comprises an scFV (claim 16).
Regarding claim 18, further to the discussion of claim 13 above, U.S. co-pending App ’007 claims suggest the nanovesicle comprises the CAR and it would be obvious to a person of ordinary skill that that it would be expressed on the surface because this is where CARs are expressed. This expression amount is structurally indistinguishable from an amount that is controlled. Regarding claim 20, further to the discussion of claim 13 above, U.S. co-pending App ’2007 claims the nanovesicle comprises Fas Ligand (claim 19).
Regarding claim 21, further to the discussion of claim 13 above, U.S. co-pending App ’007 claims the nanovesicle lacks interleukins (“knocked out” claim 7).
Regarding claim 23, further to the discussion of claim 13 above, U.S. co-pending App ’007 claims the nanovesicle comprises a bispecific CAR (claim 22).
Regarding claim 24, further to the discussion of claim 13 above, U.S. co-pending App ’007 claims the nanovesicle comprises a fusion peptide (claim 23).
Since the instant application claims are obvious over cited application claims, in view of Goh, said claims are not patentably distinct.
Claim 25 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-14, 16, 18-19 and 21-23 of copending application No. 18/571,007 (claims filed 7th, August, 2024) in view of Goh et al. (Sci Rep. 2017 Oct 30;7(1):14322.; see IDS filed 20th, March, 2022; henceforth “Goh”) as applied to claim 13 above, and in further view of Alvarez-Erviti et al. (Nat Biotechnol. 2011 Apr;29(4):341-5. Epub 2011 Mar 20.; henceforth “Alvarez-Erviti”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The teachings of U.S. co-pending App ’007 and Goh above are hereby incorporated in their entirety.
Regarding claim 25, further to the discussion of claim 13 above, U.S. co-pending App ’007 does not claim including a RVG peptide in the nanovesicle.
Nevertheless, regarding claim 25, Alvarez-Erviti teach including an RVG peptide in a nanovesicle (exosome) (abstract; pg. 341 col. 2 2nd-4th para.; Figures 1-3; pg. 342) to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.).
Therefore, regarding claim 25, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the exosome vesicles as claimed by U.S. co-pending App ’007 in view of Goh , and combine the known prior art element of the RVG peptide of Alvarez-Erviti to obtain the predicable result of a vesicle with a targeting peptide. One of ordinary skill would have been motivated to do so as taught by Alvarez-Erviti to specifically target the brain including neurons, microglia, oligodendrocytes and their precursors (pg. 343 col. 2 2nd para.). Regarding the reasonable expectation of success, Alvarez-Erviti evidences adding RVG peptides to exosomes (abstract).
Since the instant application claims are obvious over cited application claims, in view of Goh and in further view of Alvarez-Erviti, said claims are not patentably distinct.
Claims 26 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-14, 16, 18-19 and 21-23 of copending application No. 18/571,007 (claims filed 7th, August, 2024) in view of Goh et al. (Sci Rep. 2017 Oct 30;7(1):14322.; see IDS filed 20th, March, 2022; henceforth “Goh”) as applied to claim 13 above, and in further view of Nakase et al. (Sci Rep. 2017 May 16;7(1):1991.; henceforth “Nakase”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The teachings of U.S. co-pending App ’007 and Goh above are hereby incorporated in their entirety.
Regarding claim 26, further to the discussion of claim 13 above, U.S. co-pending App ’007 and Goh are silent to including a cell-penetrating peptide in the nanovesicle.
Nevertheless, regarding claim 26, Nakase teaches including cell-penetrating peptides on nanovesicles (extracellular vesicles or EVs) EVs to induce active macropinocytosis for effective cellular EV uptake (abstract; Figure 1) and to enhance cellular EV uptake (pg. 5 3rd para.).
Therefore, regarding claim 26, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the exosome as claimed by U.S. co-pending App ’007 in view of Goh, and combine the known prior art element of the cell-penetrating peptide of Nakase to obtain the predictable result of a vesicle with a cell-penetrating peptide. One of ordinary skill would have been motivated to do so as taught by Nakase to induce active macropinocytosis for effective cellular EV uptake (abstract; Figure 1) and to enhance cellular EV uptake (pg. 5 3rd para.). Regarding the reasonable expectation of success, Nakase evidences combining a cell penetrating peptide with a nanovesicle (Methods pg. 7-8).
Since the instant application claims are obvious over cited application claims, in view of Goh and Alvarez-Erviti and in further view of Nakase, said claims are not patentably distinct.
Claims 27 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-14, 16, 18-19 and 21-23 of copending application No. 18/571,007 (claims filed 7th, August, 2024) in view of Goh et al. (Sci Rep. 2017 Oct 30;7(1):14322.; see IDS filed 20th, March, 2022; henceforth “Goh”) as applied to claim 13 above, and in view of Nakase et al. (Sci Rep. 2017 May 16;7(1):1991.; henceforth “Nakase”) as applied to claim 26 above, and in further view of Arakelyan et al. (Sci Rep. 2017 May 10;7(1):1695.; henceforth “Arakelyan”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The teachings of U.S. co-pending App ’007 and Goh above are hereby incorporated in their entirety.
Regarding claim 27, further to the discussion of claims 13 and 26 above, U.S. co-pending App ’007 in view of Goh, Alvarez-Erviti and Nakase are silent to including gp120 as a cell penetrating peptide.
Nevertheless, regarding claim 27, Arakelyan teaches the peptide gp120 which is a cell-penetrating peptide that mediates attachment and fusion to target cells (abstract; see also pg. 5 2nd para.).
Therefore, regarding claim 27, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanovesicle as claimed by U.S. co-pending App ’007 in view of Goh, Alvarez-Erviti and Nakase, and combine the known prior art element of the gp120 fusion peptide of Arakelyan to obtain the predictable result of an exosome with a fusion peptide. One of ordinary skill would have been motivated to do so as taught by Arakelyan to mediate attachment and fusion to target cells (abstract; see also pg. 5 2nd para.). Regarding the reasonable expectation of success, Nakase evidences combining a cell penetrating peptide with a nanovesicle (Methods pg. 7-8).
Since the instant application claims are obvious over cited application claims, in view of Goh, Alvarez-Erviti and Nakase and in further view of Arakelyan, said claims are not patentably distinct.
Conclusion
No claim is allowable.
Correspondence
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632