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
In the reply on 26 April 2024 Applicant has amended claims 1, 3-4, 6-7, 9-12, 14-15, 17, 21, 23-25, 27-29, 31. Claims 5, 8, 13, 16, 18-20, 26, 30 and 32-40 have been cancelled. Therefore, claims 1-4, 6-7, 9-12, 14-15, 17, 21-25, 27-29, and 31 are herein pending.
Election/Restrictions
Applicant’s election of Group I (claims 1-4, 6 -7, 9-12, 14-15 and 17) drawn to a red blood cell derived extracellular vesicle loaded with a cargo, wherein the cargo comprises at least two different nucleic acid molecules in the reply filed on 26 April 2024 is acknowledged. Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement with an election that mailed on 02/03/2026. Therefore, the election response filed on 26 April 2024 will be treated without traverse (MPEP § 818.01(a)).
Claims 21-25, 27-29, and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-4, 6 -7, 9-12, 14-15 and 17 are under current examination.
Priority
This application was filed 09/29/2023 and is a 371 application of
PCT/SG2022/050187 filed on 03/31/2022, which claims benefit to the Provisional Application 63169161 filed on 03/31/2021. Thus, the earliest possible priority for the instant application is 03/31/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/20/2023 and 04/26/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action.
Abstract Objection
The abstract of the disclosure filed 09/29/2023 is objected to because the abstract is only 32 words in length, and it is not submitted as a single paragraph on a separate sheet as required. Therefore, submitted abstract is considered non-compliant.
Applicant is reminded of the proper language and format for an abstract of the disclosure. MPEP § 608.01(b)(I) sets forth guidelines for the preparation of patent abstracts. MPEP § 608.01(b)(I)(C) states that "the abstract for a national stage application filed under 35 U.S.C. 371 may be found on the front page of the Patent Cooperation Treaty publication (i.e., pamphlet). See MPEP § 1893.03(e)."
However, MPEP §608.01(b)(I) also sets forth guidelines for the abstract. MPEP § 608.01(b)(I)(C) states that “the abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.”
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Therefore, appropriate correction is required.
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 3-4 and 9 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 3 contains the trademark/trade name “Lipofectamine™ 3000™ (ThermoFisher), Turbofect™ (ThermoFisher), Lipofectamine™ MessengerMAX™ (ThermoFisher), Exofect™ (System Biosciences).
Claim 4 contains PEIMaxTM (Polysciences, Inc.) or jetPEI® (Polyplus transfection).
MPEP 2173.05(u) states that “where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982).” The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the “Lipofectamine™ 3000™, Turbofect™, Lipofectamine™ MessengerMAX™, Exofect™, PEIMaxTM or jetPEI® are used as transfection reagent, however these trademark represents the source of product rather than the identify the product composition or details. Accordingly, the trademark description is indefinite.
The rejection may be obviated by amending the claims 3-4 to recite the generic transfection reagent solution name which identifies the solution composition itself.
Claim 9 is recited a limitation “the nucleic acid molecule” of claim 6. However, claim 6 does not introduce this limitation, it has introduced “at least two different nucleic acid molecules”. Therefore, there is insufficient antecedent basis for this limitation. The rejection may be obviated by amending the claim 9 to recite “at least two different nucleic acid molecules.”
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.
Anticipated by Shi et al.
Claims 6-7, 9-11 and 14-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shi et al. (WO2020060479A1; published on 26 March 2020; cited in IDS filed 12/20/2023; hereinafter “Shi”).
With respect to claims 1-2, 6-7, 9-11, and 15, Shi describes extracellular vesicles derived from red blood cells (RBCEVs) containing a cargo comprise small molecules, siRNA, a miRNA, a gRNA, proteins, nucleic acids or components of the CRISPR/Cas9 gene editing system for the treatment of medical disorders such as a genetic disorder, inflammatory disease, cancer, autoimmune disorder, cardiovascular disease or a gastrointestinal disease (abstract, p.3 lns 1-10, p. 19 lns 6-12). Shi discloses that the cargo comprises at least two different (e.g., non-identical sequence) nucleic acid molecules (p.3 lns 24-25), wherein cargo loaded in presence of transfection reagent (e.g., Lipofection) (p. 25 lns 6-9).
With respect to claim 14, Shi discloses that the cargo further comprises a DNA repair template (p. 23 lns 4-6).
Accordingly, Shi anticipates the instant claims 6-7, 9-11 and 14-15.
Anticipated by Usman et al.
Claims 6-7, 9-11 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Usman et al. (Nat. Commun. 9, 2359, 2018; cited in IDS filed 12/20/2023; hereinafter “Usman”).
With respect to claims 6-7, 9-11, and 15, Usman describes a population of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides (ASOs), Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR–Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity (abstract, p. 2 left-hand col 2nd ¶). In figure 8 Usman shows the electroporation of Cas9 mRNA and gRNA into RBCEVs, therefore, these RBCEVs are loaded with a cargo that comprises at least two different nucleic acid molecules, an mRNA and a gRNA. These extracellular vesicles were used for genome editing by treating the leukemia cell line MOLM13 (page 12, right-hand col “Treatment of cancer cells with RBCEVs in vitro” ¶).
Accordingly, Usman anticipates the instant claims 6-7, 9-11 and 15.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 3-4, 6-7, 9-11, 14-15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al. (WO2020060479A1; published on 26 March 2020; cited in IDS filed 12/20/2023; hereinafter “Shi”), in view of Zhupanyn et al., (Journal of Controlled Release 319 (2020) 63–76; cited in IDS filed 12/20/2023; hereinafter “Zhupanyn”) and Geeurickx et al. (Nature communications, 10(1), p.3288, 2019; cited in PTO892; hereinafter “Geeurickx”).
Regarding claims 1-2, 6-7, 9-11, and 15, Shi describes extracellular vesicles derived from red blood cells (RBCEVs) containing a cargo comprise small molecules, siRNA, a miRNA, a gRNA, proteins, a plasmid, nucleic acids or components of the CRISPR/Cas9 gene editing system for the treatment of medical disorders such as a genetic disorder, inflammatory disease, cancer, autoimmune disorder, cardiovascular disease or a gastrointestinal disease (abstract, p.3 lns 1-10, p. 19 lns 6-12). Shi discloses that the cargo comprises at least two different (e.g., non-identical sequence) nucleic acid molecules (p.3 lns 24-25), wherein cargo loaded in presence of transfection reagent (e.g., Lipofection) (p. 25 lns 6-9).
With respect to claim 3, Shi does not specifically teach the transfection reagent is a Linear Polyethylenimine. However, such was known in the prior art.
Regarding claims 3-4, Zhupanyn teaches a Polyethylenimines (PEIs) are linear or branched polymers which are capable of forming non-covalent complexes with small RNA molecules including siRNAs or anti-miRs, for their delivery in vitro and in vivo (abstract) and offers a very promising strategy for the treatment of cancer (p. 64 left-hand col. 1-2nd and 4th ¶).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice the RBCEVs loaded with a cargo of Shi and include the linear Polyethylenimines as taught by Zhupanyn with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Zhupanyn because PEI-based nanoparticles with naturally occurring ECVs, thus potentially combining the beneficial properties of PEI-based complexes and of ECVs for the delivery of small RNA molecules, namely siRNAs and antimiRs (p. 64 right-hand col. 3rd¶). The POSITA would have had a reasonable expectation of success in combining the teachings of Shi and Zhupanyn because each of these teachings both successfully generated natural EVs. Therefore, the products and method as taught by Shi et al. in view of Zhupanyn et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, include the linear Polyethylenimines of Zhupanyn had a reasonable expectation of success since the steps thereof required no more than pipetting the appropriate PEIs concentration and cell culture technology.
Although Zhupanyn didn’t disclose the Linear Polyethylenimine Hydrochloride having an average molecular weight of 25,000 Da or 40,000Da, however, the rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson' s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969). The invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made as evidenced by the teachings of Shi et al. in view of Zhupanyn et al. especially in the absence of unexpected results.
Regarding claim 14, Shi discloses that the cargo further comprises a DNA repair template (p. 23 lns 4-6).
Although with respect to claim 17, Shi teaches cargo comprises a plasmid, still does not specifically teach the cargo comprises antigen-binding molecule is an antibody or an antigen-binding fragment. However, such was known in the prior art.
Regarding claim 17, Geeurickx teaches recombinant EV (rEV) will aid EV-based sample preparation and analysis, data normalization, method development and instrument calibration in various research and biomedical applications, wherein rEV comprises antibody (Fig. 1; p. 3 right-hand col 2nd ¶).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice the RBCEVs loaded with a cargo of Shi and include the antibody as taught by Geeurickx with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Geeurickx rEV will ensure rigorous sample EV analysis and is essential to advance the field and develop future EV-based biomedical applications, specifically cancer treatment (p. 9 left-hand col. 1st ¶; p. 7 right-hand col. 2nd ¶ of Geeurickx). The POSITA would have had a reasonable expectation of success in combining the teachings of Shi and Geeurickx because each of these teachings both successfully generated natural EVs. Therefore, the products and method as taught by Shi et al. in view of Geeurickx et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, include the antibody of Geeurickx had a reasonable expectation of success since the steps thereof required no more than pipetting the appropriate antibody concentration and cell culture technology.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/
Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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