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 .
Claims 1, 3-6, 8-23 and 25 are pending.
Claims 13-23 and 25 are withdrawn.
Claim 1 is amended.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/10/2025 has been entered.
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.
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, 3, 5, 6 and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over SOO (WO 2017/126939 A1) in view of WU (pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin. International Journal of Molecular Sciences. 2016.).
Regarding claim 1 and 11, SOO teaches a method of making crosslinked hyaluronic nanoparticles (abstract and claim 1). The method comprises a hyaluronic acid solution (claim 4 and 5) that is irradiated with an electron beam to produce crosslinked nanoparticles (claim 1 and 13).
Regarding claims 5 and 6, SOO teaches the size of the nanoparticle is changed using the irradiation dose of the electron beam (Page 6, paragraph 2). The increase in irradiation caused the nanoparticles to shrink in size (Page 12, paragraph 4).
Regarding claim 8, SOO teaches the concentration of aqueous solution for hyaluronic acid is 0.5 to 7% (Page 5, bullet 1).
Regarding claim 9, SOO teaches the solution is irradiated at 30 to 230 kGy (Page 6, paragraph 2).
Regarding claim 10, SOO teaches the nanoparticles had a size of 100 nm (Figure 10 and Page 11, section 7).
Regarding claim 12, SOO teaches the nanoparticles target tumors and can be loaded with doxorubicin (Page 13, Tumor Growth inhibitory Effect of Doxorubicin-Conjugated PEG-DNP).
SOO does not teach using an acidic aqueous solution with a pH between 1 and 6 or teach controlling the size of the nanoparticle by adjusting the pH of the solution.
Regarding claim 1 and 11, WU teaches a method of making hyaluronic acid nanoparticles that are used for targeting tumors and are loaded with doxorubicin (abstract). WU teaches that a lower pH value resulted in an increase in average particle size (page 4, paragraph 1). The decrease in pH allowed for the nanoparticles to swell and resulted in an increased release of the drug, doxorubicin (page 5, paragraph 3 and figure 5).
Regarding claim 3, WU teaches the hyaluronic acid solution can have a pH of 5.5, which showed an increased release rate of doxorubicin (figure 4).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using an acidic pH, such as 5.5, to increase the size of the nanoparticles. The person of ordinary skill in the art would have been motivated to make those modifications, because the decrease in pH allowed for the nanoparticles to swell and resulted in an increased release of the drug and reasonably would have expected success because the references are in the same field of endeavor, such as hyaluronic acid nanoparticles that are loaded with doxorubicin and used to target tumors.
Claims 1, 3-6 and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over SOO (WO 2017/126939 A1) and WU (pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin. International Journal of Molecular Sciences. 2016.) in view of WACH (Hydroxyl radical-induced crosslinking and radiation-initiated hydrogel formation in dilute aqueous solutions of carboxymethylcellulose. Carbohydrate Polymers. 2014.).
SOO and WU teach Applicant’s invention as discussed above. Including SOO teaching irradiating a hyaluronic acid, which is a polysaccharide, solution to promote crosslinking and WU teaching the importance of lowering the pH of the solution.
SOO and WU do not teach using HClO4 in the hyaluronic acid-containing solution.
Regarding claim 4, WACH teaches irradiating a polysaccharide solution to allow for crosslinking (abstract). WACH teaches adjusting the pH of the solution with HClO4 (page 413, paragraph 4).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using HClO4 in the hyaluronic acid-containing solution. The person of ordinary skill in the art would have been motivated to make those modifications, because acids are commonly used to adjust a pH to be more acidic and can be commonly chosen by one in the art, and reasonably would have expected success because the references are in the same field of endeavor, such as irradiating polysaccharide solutions to promote crosslinking and adjusting the pH of a solution.
Response to Arguments
Applicant argues, WACH is directed to macroscopic hydrogels and is silent with regard to the effect of pH on hyaluronic acid nanoparticles.
The Examiner finds Applicant’s argument unpersuasive, because in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this instance, as discussed in the above rejection, WACH is merely sighted to show that HClO4 can be used to adjust the pH of a solution, specifically polysaccharide solutions undergoing irradiation to promote crosslinking. Furthermore, acids are commonly used to adjust a pH to be more acidic and can be commonly chosen by one in the art
Applicant argues, SOO does not teach controlling the size of the nanoparticle by adjusting the pH of the solution.
Examiner does not find this argument persuasive, because as discussed above, although SOO does not teach controlling the size of the nanoparticle by adjusting the pH of the solution.
WU teaches a method of making hyaluronic acid nanoparticles that are used for targeting tumors and are loaded with doxorubicin (abstract). WU teaches that a lower pH value resulted in an increase in average particle size (page 4, paragraph 1). The decrease in pH allowed for the nanoparticles to swell and resulted in an increased release of the drug, doxorubicin (page 5, paragraph 3 and figure 5). WU teaches the hyaluronic acid solution can have a pH of 5.5, which showed an increased release rate of doxorubicin (figure 4).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using an acidic pH, such as 5.5, to increase the size of the nanoparticles. The person of ordinary skill in the art would have been motivated to make those modifications, because the decrease in pH allowed for the nanoparticles to swell and resulted in an increased release of the drug and reasonably would have expected success because the references are in the same field of endeavor, such as hyaluronic acid nanoparticles that are loaded with doxorubicin and used to target tumors.
Conclusion
No claims are allowable.
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/S.L.M./ Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618