DETAILED ACTION
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 10-15 are withdrawn.
Claims 1, 3, 5, 7, 9, and 16-20 are pending and represent all claims currently under consideration.
Response to Amendment
The amendment filed 03/05/2026 has been entered.
Claims 16-20 were newly added. Claims 1, 3, 5, and 7 were amended. Claims 2, 4, 6, and 8 were canceled.
The previous objection of claim 1 and rejections of claims 5 and 7 under 35 U.S.C. 112(b) are overcome by the amendment.
The previous rejections of claims 2, 3, 6, and 8 are moot, because the claims were canceled.
The objections to the specification were not addressed and are maintained.
Claims 1, 3, 5, 7, 9, and 16-20 are newly rejected under 35 U.S.C. 112.
The previous rejections of claims 1, 3, 5, 7, and 9 under 35 U.S.C. 103 have been modified to address the amendments and maintained.
Claims 16-20 are newly rejected under 35 U.S.C. 103.
Response to Arguments
Applicant's arguments filed 03/05/2026 have been fully considered but they are not persuasive.
Applicant argues that Gu does not teach the limitations of the amended claim and does not explicitly state that the agent is retained within the membrane or lumen of the extracellular vesicle (Remarks, pages 1-2, “E”). This argument is not persuasive, because Gu teaches the therapeutic agent is encapsulated in a nanoparticle (Gu, claim 7) which can be an exosome (i.e., a therapeutic agent encapsulated within a carrier; Gu, page 20, lines 4-12), and defines exosomes as a type of extracellular vesicle (i.e., the carrier comprises extracellular vesicles; Gu, page 17, line 7). While Gu does not specifically state the therapeutic agent is retained within a lumen of the extracellular vesicle, it would be prima facie obvious to one of ordinary skill in the art that if the therapeutic agent is encapsulated in an extracellular vesicle, it would be within the lumen. Gu further teaches a crosslinked network of a polymeric material (i.e., a binding agent), a small molecule agent (i.e., the therapeutic agent), and the exosome (i.e., the extracellular vesicle) in order for sustained delivery (Gu, page 19, lines 3-10), suggesting the polymeric material acts to retain the therapeutic agent. Further, as evidenced by the instant specification, sonication destabilizes the membrane, enabling the therapeutic agent to enter the lumen. Gu also teaches a sonication step (Gu, page 29, example 1), suggesting the therapeutic would be expected to enter the lumen in the same way as in the instant application.
Applicant argues that Gu in view of Prausnitz, Aravind, and Falo do not teach the limitations of the amended claim for the same reasons as above (Remarks, page 2, “F”-“H”. This argument is not persuasive for the same reasons as above.
Applicant argues that Aravind indicates that the curcumin/albumin conjugation was delivered intraperitoneally, not through a microneedle array (Remarks, page 2, “G”). This argument is not persuasive, because it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Prausnitz, Aravind, and the instant invention are all in the same field of curcumin/albumin delivery for immunotherapy. Therefore, the rejection is proper and it would have been obvious to modify the teachings of Gu and Prausnitz to utilize a conjugate of curcumin and albumin as taught by Aravind in place of the combination of curcumin and albumin taught by Prausnitz, because Aravind teaches the conjugation of curcumin to albumin has been found to increase the solubility and activity of the drugs (Aravind, abstract).
Maintained Objections to the Specification
The use of the terms Dow Corning, Sigma-Aldrich, Invitrogen, and Millipore, which are trade names or marks 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.
New 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.
Claims 1, 3, 5, 7, 9, and 16-20 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.
Regarding claim 1, there is no support in the specification for a binding agent adapted to retain the therapeutic agent. Applicant states that support for this amendment can be found in paragraph [0026] “Sonication temporarily destabilizes the EV membranes, enabling albumin to enter the EV lumens” and paragraph [0011] “Albumin is used to create additional hydrophobic binding sites to sequester curcumin, retaining it within the EVs before cell internalization, thus prolonging the bioactive lifetime of curcumin”. While this provides support for albumin, this does not provide adequate support for the general concept of “a binding agent”, which embraces compounds and a scope not previously contemplated. Further, there is no support in the instant specification for “adapting” either a binding agent or albumin.
Claims 3, 5, 7, 9, and 16-20 are dependent on claim 1, and therefore have the same deficiency.
Regarding claim 17, there is no support in the specification for the therapeutic agent being lipophilic.
Regarding claim 19, there is no support in the specification for a binding agent adapted to prevent diffusion of the therapeutic agent out of the extracellular vesicles.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 20 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 20, the terms “poor bioavailability”, “poor solubility”, and “poor stability” are relative terms which render the claim indefinite. The term “poor” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how far one can deviate before the bioavailability, solubility, or stability are considered to be poor.
Modified/Maintained 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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Gu (WO 2019200063 A1; IDS reference, 12/09/2024). The reference was cited previously by the Examiner.
Regarding claim 1, Gu teaches a skin patch comprising a microneedle array comprising a backing layer (Gu, claim 13) for the delivery of extracellular vesicles (i.e., carrier) and hair growth agents (i.e., therapeutic agents; Gu, page 1, lines 2-4). Gu further teaches the backing is a base layer of hyaluronic acid (i.e., a base material; Gu, page 7, lines 23-33), which is a hydrophilic polymer that can be biodegradable (Gu, page 21, lines 11-21) and is dissolvable in water (Gu, page 15, lines 10-11). Gu teaches the small molecule hair growth agent is encapsulated in a nanoparticle (Gu, claim 7) which can be an exosome (i.e., a therapeutic agent encapsulated within a carrier; Gu, page 20, lines 4-12). Gu teaches exosomes are embedded in the microneedle patch (i.e., the carrier is embedded within the base material; Gu, page 34, lines 16-17) and defines exosomes as a type of extracellular vesicle (i.e., the carrier comprises extracellular vesicles; Gu, page 17, line 7). Gu further teaches a crosslinked network of a polymeric material (i.e., a binding agent), a small molecule agent (i.e., the therapeutic agent), and the exosome (i.e., the extracellular vesicle) in order for sustained delivery (Gu, page 19, lines 3-10), suggesting the polymeric material acts to retain the therapeutic agent. Gu does not specifically state the therapeutic agent is within a lumen of the extracellular vesicle, but it would be prima facie obvious to one of ordinary skill in the art that if the therapeutic agent is encapsulated in an extracellular vesicle, it would be within the lumen.
Gu is considered to be analogous to the claimed invention, because both Gu and the instant invention are in the same field of microneedle arrays for therapeutic delivery. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the claimed invention based on the teachings of Gu under the meaning of 35 U.S.C. 103.
Claims 3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Gu (WO 2019200063 A1; IDS reference, 12/09/2024) as applied to claim 1, further in view of Prausnitz (US 20200238065 A1). The references were cited previously by the Examiner.
Regarding claim 3, Gu teaches all the elements of the current invention as applied to claim 1. Gu teaches the entrapment of a small molecule therapeutic agent (Gu, page 16, lines 4-5), but does not specify the small molecule as curcumin. Prausnitz, however, teaches a microneedle array for administering a substance of interest (Prausnitz, claim 1) which is dissolvable (Prausnitz, page 15, paragraph 0155) and comprises a carrier (Prausnitz, page 13, paragraph 0135) and further teaches the substance of interest can be curcumin (Prausnitz, page 11, paragraph 0111).
Gu and Prausnitz are considered to be analogous to the claimed invention, because Gu, Prausnitz, and the instant invention are all in the same field of microneedle arrays for therapeutic delivery. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Gu to include the therapeutic agent taught by Prausnitz, because both teach therapeutic delivery via microneedle array and Prausnitz demonstrates curcumin to be a suitable therapeutic agent for this method of delivery (Prausnitz, page 11, paragraph 0111).
Regarding claim 5, Gu teaches all the elements of the current invention as applied to claim 1. Gu teaches a small molecule is embedded in the exosome (i.e., extracellular vesicle; Gu, page 20, lines 9-11), but does not teach a binding agent comprising albumin. Prausnitz, however, teaches a substance of interest can be albumin (Prausnitz, page 10, paragraph 0110). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Gu to include the therapeutic agent taught by Prausnitz, because both teach therapeutic delivery via microneedle array and Prausnitz demonstrates albumin to be a suitable therapeutic agent for this method of delivery (Prausnitz, page 10, paragraph 0110).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Gu (WO 2019200063 A1; IDS reference, 12/09/2024) and Prausnitz (US 20200238065 A1) as applied to claims 1, 3, and 5, further in view of Aravind (International Immunopharmacology, 2016). The references were cited previously by the Examiner.
Regarding claim 7, Gu teaches all the elements of the current invention as applied to claim 5. As above, Gu teaches a skin patch comprising a microneedle array comprising a backing layer (Gu, claim 13) for the delivery of extracellular vesicles (i.e., carrier) and a small molecule therapeutic agent (Gu, page 16, lines 4-5). Prausnitz teaches a microneedle array for administering a substance of interest (Prausnitz, claim 1) which is dissolvable (Prausnitz, page 15, paragraph 0155) and comprises a carrier (Prausnitz, page 13, paragraph 0135) and teaches the substance of interest can be albumin (Prausnitz, page 10, paragraph 0110), curcumin (Prausnitz, page 11, paragraph 0111), or a combination (Prausnitz, page 11, paragraph 0112), but does not specify curcumin bound to albumin. Aravind, however, teaches the conjugation of curcumin to albumin has been found to increase drug solubility and activity (Aravind, abstract).
As above, Gu and Prausnitz are considered to be analogous to the claimed invention, because Gu, Prausnitz, and the instant invention are all in the same field of microneedle arrays for therapeutic delivery. As above, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Gu to include the therapeutic agent taught by Prausnitz, because both teach therapeutic delivery via microneedle array and Prausnitz demonstrates curcumin and albumin to be a suitable therapeutic agent for this method of delivery (Prausnitz, page 10-11, paragraph 0110-0112). Prausnitz, Aravind, and the instant invention are all in the same field of curcumin/albumin delivery for immunotherapy. It would have been obvious to modify the teachings of Gu and Prausnitz to utilize a conjugate of curcumin and albumin as taught by Aravind in place of the combination of substances of interest taught by Prausnitz, because Aravind teaches the conjugation of curcumin to albumin has been found to increase the solubility and activity of the drugs (Aravind, abstract).
Claim 5 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Gu (WO 2019200063 A1; IDS reference, 12/09/2024) as applied to claim 1, further in view of Falo (US 20160136407 A1). The references were cited previously by the Examiner.
Regarding claim 5, Gu teaches all the elements of the current invention as applied to claim 1. Gu teaches the small molecule is embedded in the exosome (i.e., extracellular vesicle; Gu, page 20, lines 9-11), but does not teach a therapeutic agent which is albumin. Falo teaches a dissolvable microneedle array comprising a plurality of microneedles extending from a base portion (Falo, claim 1) and teaches the delivery of ovalbumin (i.e., an albumin) as the bioactive component (i.e., therapeutic agent; Falo, page 13, paragraph 0204)
Gu and Falo are considered to be analogous to the claimed invention, because Gu, Falo, and the instant invention are all in the same field of microneedle arrays for therapeutic delivery. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Gu to use ovalbumin as the therapeutic agent, because Falo teaches ovalbumin is a well characterized model antigen (i.e., binding agent) utilized in clinical trials for microneedle arrays (Falo, page 12, paragraph 0183).
Regarding claim 9, Gu teaches all the elements of the current invention as applied to claim 1. Gu teaches a biodegradable polymer which is PLGA (Gu, page 5, lines 9-11). Falo teaches a dissolvable microneedle array comprising a plurality of microneedles extending from a base portion (Falo, claim 1) and teaches the microneedles commonly include PLGA or carboxymethylcellulose (Falo, page 5, paragraph 0102). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Gu to use CMC in place of PLGA, because Falo teaches CMC is generally preferable to PLGA as the base material of the microneedle arrays, because PLGA based devices can limit drug delivery and vaccine applications due to the relatively high temperature and vacuum required for fabrication (Falo, page 5, paragraph 0103).
New Claim Rejections - 35 USC § 103
Claims 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Gu (WO 2019200063 A1; IDS reference, 12/09/2024) as applied to claim 1, and as evidenced by Winnicka (Molecules, 2012). Gu was cited previously by the Examiner.
Regarding claim 16, Gu teaches all the elements of the current invention as applied to claim 1. Gu teaches the therapeutic agent can be ketoconazole (Gu, page 18, line 32), which is known to be lipophilic and to have hydrophobic interactions (i.e., the therapeutic agent is hydrophobic; Winnicka, page 4613, last paragraph) as evidenced by Winnicka.
Regarding claim 17, Gu teaches all the elements of the current invention as applied to claim 1. As above, Gu teaches the therapeutic agent can be ketoconazole (Gu, page 18, line 32), which is known to be lipophilic and to have hydrophobic interactions (i.e., the therapeutic agent is hydrophobic; Winnicka, page 4613, last paragraph) as evidenced by Winnicka.
Regarding claim 18, Gu teaches all the elements of the current invention as applied to claim 1. As above, Gu teaches the therapeutic agent can be ketoconazole (Gu, page 18, line 32), which is known to be lipophilic and to have hydrophobic interactions (i.e., the therapeutic agent is a hydrophobic drug; Winnicka, page 4613, last paragraph) as evidenced by Winnicka.
Regarding claim 19, Gu teaches all the elements of the current invention as applied to claim 1. As above, Gu teaches a crosslinked network of a polymeric material (i.e., a binding agent), a small molecule agent (i.e., the therapeutic agent), and the exosome (i.e., the extracellular vesicle) in order for sustained delivery (Gu, page 19, lines 3-10), suggesting it would be reasonable to expect the polymeric material acts to prevent diffusion of the therapeutic agent.
Regarding claim 20, Gu teaches all the elements of the current invention as applied to claim 1. As above, Gu teaches the therapeutic agent can be ketoconazole (Gu, page 18, line 32), which is known to be insoluble in water (i.e., is characterized by poor solubility; Winnicka, abstract) as evidenced by Winnicka.
Conclusion
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.
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/C.P.J./Examiner, Art Unit 1613
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
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