DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restriction
2. Applicant’s election without traverse of invention Group III (claims 22(a) and 23-26 drawn to an exosome comprising a nucleic acid that expresses IL-10, wherein the exosomes are isolated for size and loading of the nucleic acid that expresses IL-10) in the reply filed on 1/15/2026 is acknowledged.
3. Claims 1-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/15/2026. The amendments filed 01/15/2026 are acknowledged. Claims 1-21 are withdrawn. Claims 22-26 are pending and under examination.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted 06 April 2023 and the references cited therein have been considered, unless indicated otherwise.
Claim Rejections - 35 USC § 102
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
5. Claims 22-25 are rejected under 35 U.S.C. 102(a)(1) as being unpatentable over Bu, et al. (“Exosome-mediated delivery of inflammation-responsive Il-10 mRNA for controlled atherosclerosis treatment.” Theranostics vol. 11,20 9988-10000. 25 Oct. 2021, doi:10.7150/thno.64229)
The instant claims are directed to an exosome comprising a nucleic acid that expresses IL-10, wherein the exosomes are isolated for size and loading of the nucleic acid that expresses IL-10.
Bu, et al. teach IL-10 mRNA encapsulated into exosomes (introduction section, paragraph 3), that were isolated for loading ( isolation and characterization of exosome section) and size (results section, paragraph 2). Bu, et al. anticipate instant claim 22.
Instant claim 23 recites the exosomes are isolated from a media by at least one of: ultracentrifugation, purification, or size exclusion chromatography. Bu, et al. teach the supernatants were ultracentrifuged at 100,000g for 2 hours (isolation and characterization of exosome section). Bu, et al. further teach that current isolation methods also include size exclusion chromatography (discussion section, paragraph 6). Bu, et al. anticipate instant claim 23.
Instant claim 24 recites the exosome have a particle size ranging between 40 nm-110nm. Bu, et al. teach that exosome have a diameter of about 40-160 nm (an average about 100 nm). Although Bu, et al. do not directly teach the particle size between 40 nm-110, the range of 40-160nm taught by Bu, et al. encompasses the range taught by the Applicant.
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Regarding the limitations wherein the nucleic acid that expresses IL-10 are loaded into the exosomes by one or more electroporation steps (instant claim 25), these limitations refer to the process by which the composition is made. MPEP 2113 states that “[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). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. At 1370 ( "a product in the prior art made by a different process can anticipate a product -by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim." ). Thus, the product of Bu, et al. anticipate the product of the instant claims, even if made by a different process.
6. Claims 22-26 are rejected under 35 U.S.C. 102(a)(1) as being unpatentable over Tang, et al. (“Extracellular vesicle-encapsulated IL-10 as novel nanotherapeutics against ischemic AKI.” Science advances vol. 6,33 eaaz0748. 12 Aug. 2020, doi:10.1126/sciadv.aaz0748)
The instant claims are directed to an exosome comprising a nucleic acid that expresses IL-10, wherein the exosomes are isolated for size and loading of the nucleic acid that expresses IL-10.
Tang, et al. teach RAW 264.7 macrophages were transfected with a plasmid coding for murine IL-10 and loaded into exosomes, that were isolated based on size. Tang, et al. anticipated instant claim 22.
Instant claim 23 recites the exosomes are isolated from a media by at least one of: ultracentrifugation, purification, or size exclusion chromatography. Tang, et al. teach the extracellular vesicles, including exosomes, were isolated with ultracentrifugation at 200,000g for 2 hours (preparation of IL-10 EV’s section). Tang, et al. anticipate instant claim 23.
Instant claim 24 recites the exosome have a particle size ranging between 40 nm-110nm. Tang, et al. teach EVs had diameters ranging from 10 to 500 nm, with a mean diameter of 134 nm. Tang, et al. further teach the morphology appeared heterogeneous under a transmission electron microscope (TEM), with a mixture of both small exosome-like and large microvesicle-like particles. Although Tang, et al. do not directly teach the particle size between 40 nm-110, the range of 10-500 nm taught by Tang, et al. encompasses the range taught by the Applicant.
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Regarding the limitations wherein the nucleic acid that expresses IL-10 are loaded into the exosomes by one or more electroporation steps (instant claim 25), these limitations refer to the process by which the composition is made. MPEP 2113 states that “[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). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. At 1370 ( "a product in the prior art made by a different process can anticipate a product -by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim." ). Thus, the product of Tang et al. anticipate the product of the instant claims, even if made by a different process.
Instant claim 26 recites the exosome are autologous. Tang, et al. teach the approach of IL-10+ EV manufacturing can be applied to autologous and primary macrophages. Tang, et al. anticipate the claimed invention.
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.
7. Claim(s) 22-26 are rejected under 35 U.S.C. 103 as being unpatentable over Tang, et al. (“Extracellular vesicle-encapsulated IL-10 as novel nanotherapeutics against ischemic AKI.” Science advances vol. 6,33 eaaz0748. 12 Aug. 2020, doi:10.1126/sciadv.aaz0748) in view of Luan, et al. (“Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin. 2017 Jun;38(6):754-763. doi: 10.1038/aps.2017.12. Epub 2017 Apr 10. PMID: 28392567; PMCID: PMC5520184.”)
The instant claims are directed to an exosome comprising a nucleic acid that expresses IL-10, wherein the exosomes are isolated for size and loading of the nucleic acid that expresses IL-10.
Tang, et al. teach RAW 264.7 macrophages were transfected with a plasmid coding for murine IL-10 and loaded into exosomes, that were isolated based on size. Tang, et al. anticipated instant claim 22. Instant claim 23 recites the exosomes are isolated from a media by at least one of: ultracentrifugation, purification, or size exclusion chromatography. Tang, et al. teach the extracellular vesicles, including exosomes, were isolated with ultracentrifugation at 200,000g for 2 hours (preparation of IL-10 EV’s section). Tang, et al. anticipate instant claim 23. Instant claim 24 recites the exosome have a particle size ranging between 40 nm-110nm. Tang, et al. teach EVs had diameters ranging from 10 to 500 nm, with a mean diameter of 134 nm. Tang, et al. further teach the morphology appeared heterogeneous under a transmission electron microscope (TEM), with a mixture of both small exosome-like and large microvesicle-like particles. Although Tang, et al. do not directly teach the particle size between 40 nm-110, the range of 10-500 nm taught by Bu, et al. encompasses the range taught by the applicant. Instant claim 26 recites the exosome are autologous. Tang, et al. teach the approach of IL-10+ EV manufacturing can be applied to autologous and primary macrophages. Tang, et al. anticipate the claimed invention.
Tang, et al. does not teach the IL-10 are loaded into exosomes by one or more electroporation steps.
Although the claims limitations is a product by process limitation, Luan, et al. teach electroporation leads to superior loadings of siRNA over chemical transfection as used by Tang, et al. Luan, et al. further teach that electroporation not only enhances RNA loading into exosomes but also increase hydrophilic small molecule loading into exosome. Luan, et al. also teach that electroporation is the most common technique used to incorporated siRNA or miRNA into exosomes because this method destabilizes the vesicle membrane and allows siRNA or miRNA to penetrate vesicles.
It would be prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the exosome of Tang, et al by loading the IL-10 by electroporation as taught by Luan, et al. because Luan, et al. teach that electroporation is also a technique for loading nucleic acids in exosomes, and teaches that electroporation provides superior loading into exosomes over chemical transfection. Thus, it would be obvious to one of ordinary skill in the art to substitute the method of transfection for the method of electroporation when loading the IL-10 in the exosome, because one of ordinary skill in the art would have been able to carry out such a substitution, and the results would have yielded the predictable result of enhanced loading of the IL-10 in the exosome. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the prior art contained a product which differed from the claimed product by the substitution of some component with another component, where both components are known in the art, and one of ordinary skill in the art could have substituted one known element for another to yield predictable results, the substitution of one known element for another would have been obvious.
Pertinent Art
Angelo DePalma, PhD. “Electroporation and Competing Transfection Methods.” GEN, GEN - Genetic Engineering and Biotechnology News, 10 Oct. 2014, www.genengnews.com/insights/electroporation-and-competing-transfection-methods/.
Lamichhane TN, Raiker RS, Jay SM. Exogenous DNA Loading into Extracellular Vesicles via Electroporation is Size-Dependent and Enables Limited Gene Delivery. Mol Pharm. 2015 Oct 5;12(10):3650-7. doi: 10.1021/acs.molpharmaceut.5b00364. Epub 2015 Sep 23. PMID: 26376343; PMCID: PMC4826735.
Conclusion
8. No claims are allowed
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Syed J Abbas whose telephone number is (571)272-0015. The examiner can normally be reached M-Th, 9:00AM-4:00PM.
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/SYED J ABBAS/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674