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 .
Status of Claims
The amendments and arguments filed on 05/12/2026 are acknowledged and have been fully considered. Claims 1, 3, 5-6, 8-11, 15-17, 53-59, and 67 are now pending. Claims 2, 4, 7, 12-14, 18-52, and 60-66 are canceled; claim 1 is amended; claims 53-59 and 67 are withdrawn.
Claims 1, 3, 5-6, 8-11, and 15-17 will be examined on the merits herein.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
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.
Claims 1, 3, 6, 8-9, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over “Biosynthesis of gold nanoparticles using a kind of flavonol: Dihydromyricetin” (Guo et al., 2014) in view of “Binding of dihydromyricetin and its metal ion complexes with bovine serum albumin” (Guo, 2014), “Combined Tween 20-Stabilized Gold Nanoparticles and Reduced Graphite Oxide−Fe3O4 Nanoparticle Composites for Rapid and Efficient Removal of Mercury Species from a Complex Matrix” (Ya-Chen, 2014), and “Solubility advantage of amorphous drugs and pharmaceutical cocrystals” (Babu et al., 2011).
In regards to claim 1, Guo et al. teaches a dihydromyricetin and gold nanoparticle wherein the dihydromyricetin is directly adsorbed on the surface to the gold nanoparticles (see Gou et al., abstract).
In regards to claim 16, Guo et al. teaches that the size of the particles is varied in size, from about 25-50nm (see Guo et al., Figs. 2, 4, and 6).
Guo et al. is silent on the metal comprising iron, copper, or magnesium as well as the use of a ethoxylated sugar surfactant. Guo et al. is also silent on the nanoparticle being amorphous.
In regards to claims 1, 3, 6, and 8, Guo teaches a dihydromyricetin metal complex wherein the metal is iron (III), copper(II), magnesium, among others (see Guo, page 333, column 2, paragraph 2).
In regards to claims 1 and 9, Ya-Chen teaches that gold nanoparticles are not only stabilized by the use of Tween®, but also allow for the gold nanoparticles to suppress the nonspecific adsorption of macromolecules such as a proteins and DNA (see Ya-Chen, page 17438, column 1, paragraph 2). Tween® is taught as a tradename of ethoxylated sugar-based surfactants in the specification as filed (see page 12, paragraph 3 of the instant specification as filed).
In regards to claims 1, Babu teaches that amorphous phases of drugs have enhanced solubility (see Babu, abstract) and are able to dissolve faster compared to crystalline forms (see Babu, page 2664, column 2, paragraph 2). Babu also teaches that an amorphous nanoparticle is known to have better bioavailability for multiple drugs as compared to a crystalline structure (see Babu, paragraph bridging pages 2667-2668 and the following paragraph).
In regards to claims 1, 3, 6, 8-9, and 16, it would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of Guo et al., Guo, Ya-Chen, and Babu to formulate an amorphous nanoparticle comprising a dihydromyricetin and different metals, such as iron(III), copper(II), and magnesium, in a complex as it is known that different dihydromyricetin-metal complexes can change the transport, disposition, and pharmacological effects of free dihydromyricetin (see Guo, page 340, column 2, conclusion) and the Tween® of Ya-Chen to help stabilize the nanoparticles. Further, it would be obvious to one with ordinary skill in the art to formulate an amorphous nanoparticle comprising a dihydromyricetin and metal complex using amorphous dihydromyricetin as amorphous drugs have a better solubility and are able to dissolve faster (see Babu, abstract; page 2664, column 2, paragraph 2) and that amorphous nanoparticles are known to have better bioavailability (see Babu, paragraph bridging pages 2667-2668 and the following paragraph). One with ordinary skill in the art would be motivated to combine the dihydromyricetin nanoparticle of Guo et al. with the different dihydromyricetin-metal complexes of Guo, stabilizer of Ya-Chen, and the amorphous nanoparticle of Babu according to the method of making nanoparticles using dihydromyricetin (see Guo et al., page 128, synthesis of gold nanoparticles using DMY) to yield predictable results with a reasonable expectation of success. One with ordinary skill in the art would be motivated to combine prior art elements according to known methods to yield predictable results.
Further, as the term “core” has not been described in detail or given a specific definition in the specification or claims other than a solid core (see specification as filed, page 9, final paragraph), it would be within the purview of one with ordinary skill in the art to understand that a gold nanoparticle itself is the core using the broadest reasonable interpretation of the term “core”.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over “Biosynthesis of gold nanoparticles using a kind of flavonol: Dihydromyricetin” (Guo et al., 2014) in view of “Binding of dihydromyricetin and its metal ion complexes with bovine serum albumin” (Guo, 2014), “Combined Tween 20-Stabilized Gold Nanoparticles and Reduced Graphite Oxide−Fe3O4 Nanoparticle Composites for Rapid and Efficient Removal of Mercury Species from a Complex Matrix” (Ya-Chen, 2014), and “Solubility advantage of amorphous drugs and pharmaceutical cocrystals” (Babu et al., 2011) as applied to claims 1, 3, 6, 8-9, and 16 above, and further in view of US PGPUB 20140302154 A1 (Waldoefner, 2014).
The teachings of Guo et al., Guo, Ya-Chen, and Babu have been described supra.
The combination of Guo et al., Guo, Ya-Chen, and Babu are silent on the use of iron(II) in the complex.
In regards to claim 5, Waldoefner teaches that iron(II) and iron(III) compounds of the same anion, such as iron (II) nitrate and iron(III) nitrate, can be used in nanoparticles (see Waldoefner, paragraphs 0032-0034).
In regards to claim 5, it would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of Guo et al., Guo, Ya-Chen, and Babu with Waldoefner to formulate a nanoparticle comprising a dihydromyricetin and iron(II) metal complex as it is known that compounds of iron(II) and iron(III) with the same anion can be used in nanoparticles. Further, it is known that different dihydromyricetin-metal complexes can change the transport, disposition, and pharmacological effects of free dihydromyricetin (see Guo, page 340, column 2, conclusion). It would be obvious to one with ordinary skill in the art at the time of the effective filing date to combine the nanoparticle of Guo et al., Guo, Ya-Chen, and Babu with the iron(II) cation of Waldoefner according to the method of making nanoparticles using dihydromyricetin (see Guo et al., page 128, synthesis of gold nanoparticles using DMY) to yield predictable results with a reasonable expectation of success. One with ordinary skill in the art would be motivated to combine prior art elements according to known methods to yield predictable results.
Claims 11, 15, 17 are rejected under 35 U.S.C. 103 as being unpatentable over “Biosynthesis of gold nanoparticles using a kind of flavonol: Dihydromyricetin” (Guo et al., 2014) in view of “Binding of dihydromyricetin and its metal ion complexes with bovine serum albumin” (Guo, 2014), “Combined Tween 20-Stabilized Gold Nanoparticles and Reduced Graphite Oxide−Fe3O4 Nanoparticle Composites for Rapid and Efficient Removal of Mercury Species from a Complex Matrix” (Ya-Chen, 2014), and “Solubility advantage of amorphous drugs and pharmaceutical cocrystals” (Babu et al., 2011) as applied to claims 1, 3, 6, 8-9, and 16 above, and further in view of US PGPUB 20190192444 A1 (Barzilay, 2019).
The teachings of Guo et al., Guo, Ya-Chen, and Babu have been described supra.
The combination of Guo et al., Guo, Ya-Chen, and Babu is silent on the use hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, cyclodextrin, an enteric coating, or an oral dosage form comprising the nanoparticle.
In regards to claims 11, 15, and 17, Barzilay teaches a microparticle oral composition, such as a tablet or capsule (see Barzilay, paragraphs 0010 and 0039), comprising dihydromyricetin as a dietary supplement (see Barzilay, paragraph 0137) and an enteric coating such as hydroxypropylmethyl cellulose acetate succinate, hydroxypropyl methylcellulose, cyclodextrin (see Barzilay, paragraph 0034; paragraph 0086).
In regards to claims 11, 15, and 17, it would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of Guo et al., Guo, Ya-Chen, and Babu with the teachings of Barzilay to formulate a tablet or capsule comprising the nanoparticle composition comprising a dihydromyricetin and metal complex and a stabilizer such as hydroxypropylmethyl cellulose acetate succinate, hydroxypropyl methylcellulose, or cyclodextrin as the enteric ingredient prevents the dissolution or disintegration of the dietary supplement in the mouth or the proximal sites in the gastric environment (see Barzilay, paragraph 0123). One with ordinary skill in the art would be motivated to combine the nanoparticle Guo et al., Guo, Ya-Chen, and Babu with the oral composition of Barzilay according to the method of making an oral composition comprising dihydromyricetin and an enteric ingredient (see Barzilay, paragraphs 257-266) to yield predictable results with a reasonable expectation of success. One with ordinary skill in the art would be motivated to combine prior art elements according to known methods to yield predictable results.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over “Biosynthesis of gold nanoparticles using a kind of flavonol: Dihydromyricetin” (Guo et al., 2014) in view of “Binding of dihydromyricetin and its metal ion complexes with bovine serum albumin” (Guo, 2014), “Combined Tween 20-Stabilized Gold Nanoparticles and Reduced Graphite Oxide−Fe3O4 Nanoparticle Composites for Rapid and Efficient Removal of Mercury Species from a Complex Matrix” (Ya-Chen, 2014), and “Solubility advantage of amorphous drugs and pharmaceutical cocrystals” (Babu et al., 2011) as applied to claims 1, 3, 6, 8-9, and 16 above, and further in view of US PGPUB 20170209386 A1 (Pagels, 2017)
The teachings of Guo et al., Guo, Ya-Chen, and Babu have been described supra.
The combination of Guo et al., Guo, Ya-Chen, and Babu is silent on the use polystyrene-block-polyethylene glycol in the composition.
In regards to claim 10, Pagels teaches the use of polystyrene-block-poly(ethylene glycol) as a coating for nanoparticles (see Pagels, paragraph 0018, 0082).
In regards to claim 10, it would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of Guo et al., Guo, Ya-Chen, and Babu with the teachings of Pagels to formulate nanoparticle comprising dihydromyricetin and a metal complex coated with polystyrene-block-poly(ethylene glycol) as the coating can modify the surface properties of the particle to make it stable in an aqueous environment. It would be obvious to one with ordinary skill in the art to combine the nanoparticle of Guo et al., Guo, Ya-Chen, and Babu with the coating of Pagels to formulate a nanoparticle comprising a dihydromyricetin and metal complex with a coating to make it stable in an aqueous environment according to the known method of coating a nanoparticle (see Pagels, paragraph 0084) to yield predictable results with a reasonable expectation of success. One with ordinary skill in the art would be motivated to combine prior art elements according to known methods to yield predictable results.
Response to Arguments
Applicant's arguments filed 02/05/2026 and 05/12/2026 have been fully considered but they are not persuasive.
In regards to applicant’s argument that the teachings of Guo et al., Guo, Ya-Chen, and Babu do not teach a nanoparticle that is amorphous with a core comprising dihydromyricetin complexed with a metal, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the instant case, Guo et al. teaches dihydromyricetin and gold nanoparticle wherein the dihydromyricetin is directly adsorbed on the surface to the gold nanoparticles (see Gou et al., abstract) and Guo teaches that the metals are known to be complexed with the dihydromyricetin (see Guo, page 333, column 2, paragraph 2). Further, as the term “core” has not been described in detail or given a specific definition in the specification or claims other than a solid core (see specification as filed, page 9, final paragraph), it would be within the purview of one with ordinary skill in the art to understand that a gold nanoparticle itself is the core using the broadest reasonable interpretation of the term “core”.
Applicant further argues that Babu does not teach amorphous nanoparticles, rather only portions of the nanoparticle are amorphous and others are nanocrystalline, it is pointed out that Babu does direct comparisons between nanocrystalline and amorphous nanoparticles (see Babu, Figure 7., page 2667-2668, Itraconazole-Solubility Trends; page 2666, Cefuroxime Axetil (CFA). Continuing on, applicant argues that the chemical structure of dihydromyricetin is different from itraconazole, however it is pointed out that itraconazole is not the only drug that is tested and shown to have better dissolution rates in the amorphous form (i.e., cefuroxime axetil, indomethacin (see Babu, page 2667, Indomethacin), which have different structures as well. It would be within the purview of one with ordinary skill in the art to understand that the amorphous form of a drug in general has better dissolution rates when compared to the nanocrystalline form using the teachings of Babu.
Applicant also argues that the nanoparticle of Ya-Chen is nanocrystalline and by changing the form to being amorphous would render the nanoparticle unsatisfactory for its intended purpose, however it is noted that the teachings of Ya-Chen are used to show why it would be obvious to one with ordinary skill in the art to use Tween-20® for example in a metal nanoparticles specifically, not necessarily for the mercury absorbing purpose of the nanoparticles. The benefit of using Tween® is taught in Ya-Chen as allowing for the gold nanoparticles to suppress the nonspecific adsorption of macromolecules such as a proteins and DNA (see Ya-Chen, page 17438, column 1, paragraph 2).
As such, it would be within the purview of one with ordinary skill in the art to use the teachings of Babu to modify the teachings of Guo et al. with the teachings of the other references to use amorphous nanoparticle over the crystalline structure discussed in Guo et al. as the amorphous nanoparticle has better bioavailability. One with ordinary skill in the art would be motivated to combine the dihydromyricetin nanoparticle of Guo et al. with the different dihydromyricetin-metal complexes of Guo, stabilizer of Ya-Chen, and the amorphous nanoparticle of Babu according to the method of making nanoparticles using dihydromyricetin (see Guo et al., page 128, synthesis of gold nanoparticles using DMY) to yield predictable results with a reasonable expectation of success. One with ordinary skill in the art would be motivated to combine prior art elements according to known methods to yield predictable results.
In regards to the applicant’s arguments against the rejections of claims 5, 10-11, 15, and 17, there are no additional arguments made and applicant’s arguments are not persuasive and have been rebutted, the rejections are maintained.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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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/ISIS A GHALI/Primary Examiner, Art Unit 1611
/A.A.A./Examiner, Art Unit 1611
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