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
1. The amendment filed 11/17/2025 has been entered. Claims 1 – 2, 9 – 10, 12, 14, 16, and 18 – 19 and new claims 21 – 27 are pending. Claims 3 – 8, 11, 13, 15, 17, and 20 have been canceled.
Priority
2. This application is a 35 U.S.C. § 371 national stage application of PCT International Application No. PCT/US2021/023320, filed on March 19, 2021, which claims the benefit of U.S. Provisional Application Nos. 62/992,907, filed on March 21, 2020, 62/994,838, filed on March 25, 2020; 62/994,843, filed on March 26, 2020, and 62/994,863, filed on March 26, 2020.
Maintained Specification Objection
3. The use of the term Knockout, Glutamax, mTeSR, TrypLE, Lipidure, Neurobasal-A, B27, E8 medium, Matrigel, PhosStop, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Withdrawn Claim Objections
4. The objection to claim 2 is withdrawn in view of Applicant’s amendment to the claim.
5. The objection to claim 5 is rendered moot in view of Applicant’s cancelation of the claim.
6. The objection to claim 13 is rendered moot in view of Applicant’s cancelation of the claim.
7. The objection to claim 15 is rendered moot in view of Applicant’s cancelation of the claim.
8. The objection to claim 16 is withdrawn in view of Applicant’s amendment to the claim.
Withdrawn Claim Rejections - 35 USC § 112
9. The rejection of claims 3 – 8, 11, 13, 15, 17, and 20 under 35 U.S.C. 112(a) is rendered moot in view of Applicant’s cancelation of these claims.
10. The rejection of claims 1 – 2, 9 – 10, 12, 14, 17, and 18 – 19 under 35 U.S.C. 112(a) is withdrawn in view of Applicant’s amendment to claim 1.
11. The rejection of claims 3 – 8, 11, 13, 15, 17, and 20 under 35 U.S.C. 112(b) is rendered moot in view of Applicant’s cancelation of these claims.
12. The rejection of claims 1 – 2, 9 – 10, 12, 14, 17, and 18 – 19 under 35 U.S.C. 112(a) is withdrawn in view of Applicant’s amendment to the claims.
Claim Objections and Rejections Necessitated by Amendment
Claim Objections
13. Claim 18 is objected to because of the following informalities: in line 5, “engineered or loaded exosomes” should read “engineered exosomes” because claim 1 does not recite “loaded exosomes”. Appropriate correction is required.
14. Claim 21 is objected to because the claim does not end in a period. Each claim must begin with a capital letter and end with a period.
15. Claim 22 is objected to because the claim does not end in a period. Each claim must begin with a capital letter and end with a period.
16. Claim 23 and 24 are objected to because of the following informalities: in line 2, “with NFkappaB Inhibitor” should read “with an NFkappaB inhibitor”. Appropriate correction is required.
17. Applicant is advised that should claim 23 be found allowable, claim 24 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
18. Claim 23 and 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. 37 CFR 1.118 (a) states that “No amendment shall introduce new matter into the disclosure of an application after the filing date of the application”.
Claims 23 and 24 are drawn to the method of claim 10, wherein the purified hypothalamus exosomes are loaded with NFkappaB Inhibitor. Claims 23 and 24 depend from claim 10 and claim 10 depends from claim 9. Claims 9 and 10 recite the one or more therapeutic agents comprise one or more nucleic acids.
The specification provides no implicit or explicit support for the context of an exosome loaded with a nucleic acid that is an NFkappaB inhibitor. The specification has only provided support for exosomes loaded with small molecule chemical inhibitors of NFkappaB at page 50 – 51, para. 217, and Figure 22. Applicants are reminded that it is their burden to show where the specification supports any amendments to the claims. See 37 CFR 1.121 (b)(2)(iii), the MPEP 714.02, 3rd paragraph, last sentence and also the MPEP 2163.07, last sentence.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application. MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure [or point to case law supporting incorporation of such a limitation as in the instant case]” (emphasis added).
Claim Rejections - 35 USC § 112
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.
19. Claims 21 – 24 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.
20. Regarding claim 21, “wherein loading” is not recited in claim 10 and therefore lacks antecedent basis.
21. Claim 22 depends from claim 10 and claim 10 recites “where the nucleic acid is DNA, messenger RNA, micro RNA, or small interfering RNA”. However, claim 22 recites “the purified hypothalamus exosomes are loaded with IL-6”. It is unclear if claim 22 means that the exosomes are loaded with IL-6 or are loaded with a nucleic acid that expresses IL-6 or a nucleic acid that inhibits expression of IL-6.
22. Claim 23 and 24 depend from claim 10 and claim 10 recites “where the nucleic acid is DNA, messenger RNA, micro RNA, or small interfering RNA”. However, claim 23 and 24 recite “the purified hypothalamus exosomes are loaded with NFkappaB Inhibitor”. It is unclear if claims 23 – 24 mean that the exosomes are loaded with NFkappaB inhibitor or are loaded with a nucleic acid that expresses a NFkappaB inhibitor or a nucleic acid that inhibits expression of a NFkappaB inhibitor.
Claim Interpretation
23. For the purpose of applying prior art, “hypothalamus exosomes” of claim 1 is interpreted to comprise exosomes from a human hypothalamus and exosomes isolated from human hypothalamus cells where the cells are cells isolated from a human hypothalamus or human pluripotent cells directed to differentiate to hypothalamus cells. Applicant’s specification does not provide a definition of “hypothalamus exosomes”. However, Applicant’s specification discloses Example 4 where human pluripotent stem cells were differentiated into hypothalamic stem cells and Example 5 where exosomes were secreted from these hypothalamic stem cells (page 35 – 36).
24. For the purpose of applying prior art, claim 2 is interpreted as a product-by-process claim where the claim is not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113.
25. For the purpose of applying prior art, claim 21 is interpreted as a product-by-process claim where the claim is not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113.
26. For the purpose of applying prior art, claim 22 is interpreted as a product-by-process claim where the claim is not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113.
27. For the purpose of applying prior art, claim 22 is interpreted as the exosomes are loaded with an siRNA targeting IL-6 based on Applicant’s specification at page 50, para. 215 and Figure 21.
28. For the purpose of applying prior art, claims 23 – 24 are interpreted to depend from claim 1 where the therapeutic agent inhibits NF[Symbol font/0x6B]b based on Applicant’s specification at page 9, para. 60 and Figure 22.
29. For the purpose of applying prior art, claim 25 is interpreted as a product-by-process claim where the claim is not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
30. Claim(s) 1, 2, 9, 10, 14, 16, 18, 19, 21, 22, 25, and 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Zhang, Yalin, et al. Nature 548.7665 (2017): 52-57.), hereinafter Zhang as evidenced by Al-Ansari (Al-Ansari, Mysoon M., et. al. Oncotarget 6.30 (2015): 30006), hereinafter Al-Ansari in view of Rhee (KR-20180005546-A; Filed 07/06/2016; Published 01/16/2018), hereinafter Rhee. A machine translation of KR20180005546A is provided. The translation was performed on 12/19/2025 of pages 3 – 10 of the original document.
Regarding claim 1, 2, and 25, Zhang teaches administering 100 ng of exosomes secreted by hypothalamus neural stem/progenitor cells (htNSCs) from the hypothalamus in mid-aged mice via a hypothalamic third-ventricle cannula (“administering” and “parenteral route” and “subject suffering from inflammation” and “therapeutically effective amount” and “hypothalamus exosomes” “of claim 1, 2, and 25) helped maintain htNSCs and reduced hypothalamic inflammation (“inflammation”) (page 54, right col.; page 56, left col and right col. para. 1; Figure 6b; page 58, left col. para. 2; page 59, left col. para. 3; Extended Data Figure 4, 5, 6, 9 – 10). Zhang teaches the exosomes are produced from hypothalamic neural stem cells and purified by ultracentrifugation, washing, and filtering, and analyzed by immunoblot, flow cytometry, nanoparticle tracking, density-gradient ultracentrifugation, pull-down assay, and real-time PCR (“purified” of claim 1) (page 54, right col.; page 58, left col. para. 1 and right col. para. 2). Zhang does not teach “a human subject” or “human hypothalamus exosomes” of claim 1.
Regarding “engineered to deliver one or more therapeutic agents” of claim 1, “nucleic acid” of claim 9, and “micro RNA” of claims 10 and 21, Zhang teaches microRNAs (miRNAs) are present in the exosomes and these miRNAs are transferrable among htNSCs (page 54, right col.; page 56, left col. and right col. para. 1; Figure 4d). However, Zhang does not teach “engineered” of claim 1.
Regarding claim 16 and 18, Zhang teaches administering 100 ng (0.0001 mg) (claim 18) of purified exosomes per subject (“liquid” of claim 16) (page 59, left col. para. 3; Extended Data Figure 10) but does not teach a dose recited in claim 18.
Regarding claim 19, Zhang teaches administering the exosomes three times per week for a duration of 3 – 4 months in mid-aged mice helped maintain htNSCs and that this effect was associated with a reduction in hypothalamic inflammation (“at least 1, 2, 3, or 4 weeks after the inflammation” and “multiple doses”) (page 56, left col.; Figure 6; Extended Data Figure 10a; page 59, left col. para. 3).
Regarding claim 22, Zhang teaches the exosomal miRNA146b-5p and the exosomes reduce the level of IL-6 (page 55, left col. para. 2; Figure 5; Extended Data Figure 6 and 10a). miRNA 146b-5p inhibits IL-6 expression through a specific sequence at the IL-6 3’-UTR as evidenced by Al-Ansari (Abstract; page 30008, right col. para. 2; Figure 3).
Zhang does not teach “a human subject” or “human hypothalamus exosomes” or “engineered” of claim 1 or “a degenerative disease” of claim 14 or a dose recited in claim 18 or “biocompatible scaffold that is a hydrogel” of claim 27. However, Zhang teaches htNSCs secrete the exosomes that reduce hypothalamic inflammation (page 58, left col. para. 1 and right col. para. 2). Zhang teaches hypothalamic stem/progenitor cells contributed greatly to exosomal miRNAs in cerebrospinal fluid and these exosomal miRNAs declined during aging whereas treatment with healthy hypothalamic stem/progenitor cell-excreted exosomes led to the slowing of aging (Abstract). Zhang teaches adult neural stem/progenitor cells are present in the hypothalamus, in particular in the mediobasal hypothalamic region (MBH), which is crucial for the neuroendocrine regulation of the physiological homeostasis of the whole body (page 52, left col. para. 1). Zhang teaches ablating htNSCs in the hypothalamic third-ventricle wall of the MBH in mice where these mid-aged mice showed accelerated decreases in muscle endurance, coordination, treadmill performance, sociality and novel object recognition (page 52, right col. para. 2; page 53, left col. para. 1). Zhang teaches htNSCs implanted in the MBH where htNSCs were ablated did not survive which may be related to related to an inflammatory hypothalamic environment, which is harmful for htNSCs (page 54, left col. para. 2). Zhang teaches inhibition of the inflammatory response due to htNSC ablation by implanting htNSCs stably expressing dominant-negative I[Symbol font/0x6B]Bα but implantation of mesenchymal stem cells showed not effects (page 54, left col. para. 2; Figure 3a; Figure 3c; page 54, left col. para. 2).
Regarding “a human subject” or “human” exosomes or “engineered” of claim 1 and “degenerative disease” of claim 14, Rhee teaches parenteral administration of a pharmaceutical composition comprising human exosomes engineered to deliver siRNA (“a human subject”, “human” exosomes, “engineered” of claim 1) to humans for treating various diseases including osteoarthritis (“degenerative disease” of claim 14) (page 5, 0013 – 0016; page 6, para. 0017 – 0019; page 7, 0019 – 0021; page 8, para. 0024 – 0025; page 9, para. 0026 – 0027; page 12, para. 0040; Figure 1, 5 – 7; page 27, para. 0086). Rhee teaches the exosomes can be delivered intracerebrovascularly (page 9, para. 0027). Rhee teaches loading siRNA for silencing miR-34a into exosomes for delivery of cells to maintain Type II collagen and decrease expression of miR-34a thereby suppressing osteoarthritis (page 4, 0009 – 0010).
Regarding claim 18, Rhee teaches the dosage varies depending on the condition and weight of the subject, the degree of disease, the drug form, the route and period of administration, and can be appropriately selected by a person skilled in the art (page 9, 0028).
Regarding claim 27, Rhee teaches the exosomes may be in a composition comprising gelling agents and can be provided in the form of any formulation suitable for topical application such as a gel (page 11, para. 0036 – 0037).
Rhee teaches there is a need to develop new treatments and treatment methods that can maximize the therapeutic efficacy for various diseases, including osteoarthritis, by actively utilizing exosomes (page 3, para. 0006).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Zhang regarding a method of treating inflammation with purified hypothalamus exosomes containing nucleic acids with the teachings of Rhee regarding a method of treating osteoarthritis with a pharmaceutical composition comprising exosomes derived from human cells where the exosomes are engineered to deliver siRNA to arrive at the claimed method comprising administering by oral or parenteral route to a human subject suffering from inflammation a pharmaceutical composition comprising a therapeutically effective amount of purified human hypothalamus exosomes and wherein the purified human hypothalamus exosomes are engineered to deliver one or more therapeutic agents. One would have been motivated to combine the teachings of Zhang and Rhee in a method for treating inflammation as Rhee teaches there is a need to develop new treatments and treatment methods that can maximize the therapeutic efficacy for various diseases, including osteoarthritis, by actively utilizing exosomes. One would have a reasonable expectation of success in combining the teachings as Zhang teaches the exosomes reduced inflammation and Rhee teaches the exosomes with siRNA reduce miR34-a levels to maintain Type II collagen thereby suppressing osteoarthritis.
31. Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Zhang, Yalin, et al. Nature 548.7665 (2017): 52-57.), hereinafter Zhang as evidenced by Al-Ansari (Al-Ansari, Mysoon M., et. al. Oncotarget 6.30 (2015): 30006), hereinafter Al-Ansari in view of Rhee (KR-20180005546-A; Filed 07/06/2016; Published 01/16/2018), hereinafter Rhee as applied to claims 1, 2, 9, 10, 14, 16, 18, 19, 21, 22, 25, and 27 above, and further in view of Kim (Kim, Seon Hee, et al. The Journal of Immunology 179.4 (2007): 2242-2249.), hereinafter Kim. A machine translation of KR20180005546A is provided. The translation was performed on 12/19/2025 of pages 3 – 10 of the original document.
Zhang in view of Rhee make obvious the limitations of claim 1 as set forth above. Zhang teaches the htNSCs secrete IL-2 and IL-7 in Extended Data Figure 7. Rhee teaches the exosome is loaded with a drug for treating, suppressing or preventing a target disease where the drug is delivered to target cells and the drug may be one or more selected from various proteins, peptides, and nucleic acids and compounds having various pharmacological activities are also included in the category of drugs (page 5, para. 0014 – 0016; page 6, para. 0019; page 7, 0019). Rhee does not teach “cytokine”, “interleukin”, “interferon” of claim 12.
Kim teaches exosomes isolated from cells modified to express IL-4 showed membrane-associated IL-4 in the exosomes (page 2246, left col. para. 1; Figure 2B). Kim teaches these exosomes significantly suppressed paw swelling in an animal model of inflammation (page 2246, left col. para. 2 and right col. para. 1; Figure 3). Kim teaches the exosomes reverse established arthritis and that the use of exosomes derived from immunosuppressive cells for treatment of autoimmune disease may be safer as well as more effective that using modified cells (page 2243, left col. para. 2 and right col. para. 1; page 2249, left col. para. 2). Kim teaches IL-4 exhibits anti-inflammatory effects and injection of recombinant IL-4 protein has been shown to be therapeutic in mouse models of autoimmune disease including collagen-induced arthritis, type I diabetes, and experimental autoimmune encephalomyelitis (page 2242, left col. para. 1).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Zhang regarding a method of treating inflammation with purified hypothalamus exosomes with the teachings of Rhee regarding a method of treating osteoarthritis with a pharmaceutical composition comprising exosomes derived from human cells with the teachings of Kim regarding exosomes with membrane associated IL-4 suppress inflammation to arrive at the claimed method where the one or more therapeutic agents comprise IL-4. One would have been motivated to combine the teachings of Zhang, Rhee, and Kim in a method for treating inflammation as Rhee teaches there is a need to develop new treatments and treatment methods that can maximize the therapeutic efficacy for various diseases, including osteoarthritis, by actively utilizing exosomes and Kim teaches IL-4 has been shown to be therapeutic in models of autoimmune disease including arthritis. One would have a reasonable expectation of success in combining the teachings as Kim teaches the exosomes reversed established arthritis and that the use of exosomes derived from immunosuppressive cells for treatment of autoimmune disease may be safer as well as more effective that using modified cells.
32. Claim(s) 23, 24, and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Zhang, Yalin, et al. Nature 548.7665 (2017): 52-57.), hereinafter Zhang as evidenced by Al-Ansari (Al-Ansari, Mysoon M., et. al. Oncotarget 6.30 (2015): 30006), hereinafter Al-Ansari in view of Rhee (KR-20180005546-A; Filed 07/06/2016; Published 01/16/2018), hereinafter Rhee as applied to 1, 2, 9, 10, 14, 16, 18, 19, 21, 22, 25, and 27 above, and further in view of Zhuang (Zhuang, Xiaoying, et al. Molecular Therapy 19.10 (2011): 1769-1779.), hereinafter Zhuang as evidenced by Olivera (Olivera A, et. al. Int Immunopharmacol. 2012 Feb;12(2):368-77), hereinafter Olivera in view of Unlap (Unlap MT, et. al. Brain Res Mol Brain Res. 1997 Apr;45(1):83-9), hereinafter Unlap.
Zhang in view of Rhee make obvious the limitations of claim 1 as set forth above. Zhang and Rhee do not teach exosomes loaded with an NFkappaB inhibitor of claims 23 and 24 or “dexamethasone” of claim 26. However, Zhang teaches htNSCs expressing I[Symbol font/0x6B]Bα survived when implanted in mid-aged mice and improved their survival relative to control htNSCs (page 54, left col. para. 2; Figure 3). Zhang teaches htNSCs expressing I[Symbol font/0x6B]Bα are resistant to NF-[Symbol font/0x6B]B-mediated inflammation (page 54, left col. para. 2). Rhee teaches there is a need to develop new treatments and treatment methods that can maximize the therapeutic efficacy for various diseases, including osteoarthritis, by actively utilizing exosomes (page 3, para. 0006).
Regarding claims 23 and 24, Zhuang teaches encapsulating curcumin within exosomes and administering these exosomes to inflammation disease models, where the exosomes protected against inflammation (Abstract; page 1772; Figure 4; page 1773, right col., para. 2; Figure 5; page 1777, left col. and right col. last para.). Zhuang teaches despite the development of drugs that preferentially target inflammatory cells without harming normal tissues, delivery of these drugs to the brain remains a major challenge because of the difficulty in penetrating the blood-brain barrier (page 1769, left col.). Zhuang teaches exosome encapsulated curcumin leads to significantly increased solubility, stability, and bioavailability of the encapsulated curcumin (page 1769, right col. para. 1; page 1771, left col. para. 2; Figure 2). Zhuang teaches curcumin is a powerful anti-inflammatory agent (page 1776, left col. para. 3). Curcumin is an inhibitor of NFkappaB as evidenced by Olivera (Abstract; page 2, last para.). Zhuang does not teach “dexamethasone” of claim 26.
Regarding “dexamethasone” of claim 26, Unlap teaches dexamethasone inhibits NF[Symbol font/0x6B]B binding in rat brain (Abstract; page 84, left col. para. 3; page 85, right col. para. 2). Unlap teaches dexamethasone can increase I[Symbol font/0x6B]Bα levels which is a protein that binds NF[Symbol font/0x6B]B to inhibit its transcription factor activity (page 84, left col. para. 2; page 87, right col. last para.).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Zhang regarding a method of treating inflammation with purified hypothalamus exosomes with the teachings of Rhee regarding a method of treating disease with a pharmaceutical composition comprising exosomes derived from human cells with the teachings of Zhuang regarding a method of treating inflammation with exosomes loaded with curcumin that is a NFkappaB inhibitor with the teachings of Unlap regarding dexamethasone is a NFkappaB inhibitor to arrive at the claimed method where the purified hypothalamus exosomes are loaded with an NFkappaB inhibitor that is dexamethasone. One would have been motivated to combine the teachings of Zhang, Rhee, Zhuang, and Unlap in a method for treating brain inflammation as Rhee teaches there is a need to develop new treatments and treatment methods that can maximize the therapeutic efficacy for various diseases by actively utilizing exosomes and Zhuang teaches exosome encapsulated curcumin leads to significantly increased solubility, stability, and bioavailability of the encapsulated curcumin. One would have a reasonable expectation of success in combining the teachings as both curcumin and dexamethasone are NFkappaB inhibitors and Zhuang teaches the curcumin-loaded exosomes protected against inflammation and Unlap teaches dexamethasone inhibits NFkappaB binding in the brain.
Applicant’s Arguments/ Response to Arguments
33. Applicant Argues: On page 7 – 8, Applicant asserts that claim 1 has been amended to resolve the issues regarding the 112(a) scope of enablement rejection.
Response to Argument: The rejection has been withdrawn.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZANNA M BEHARRY whose telephone number is (571)270-0411. The examiner can normally be reached Monday - Friday 8:45 am - 5:45 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571)272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Z.M.B./Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632