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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 November 24, 2025, that includes a response to the Final Office Action mailed June 24, 2025, has been entered. Claims 12-20, 23-25, and 28-56 have been canceled. Claims 2-5, 8-10, 27, and 59-61 have been withdrawn. Claims 1, 6, 7, 11, 21, 22, 26, 57, and 58 are under examination.
Claim Rejections - 35 USC § 103 (I and II)
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.
I. Claims 1, 6, 7, 11, 21, 22, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Qiao et al. (Langmuir. 2011; 27: 11090-11097).
I. Applicant Claims
Applicant claims a particle comprising gold nanoparticles and sodium cholate; wherein the sodium cholate is present in the amount of about 70-99 wt%.
I. Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Qiao et al. disclose a particle consisting essentially of a core of gold nanoparticles, and sodium cholate as a capping agent; wherein the particle is formed by reacting e.g. 1.0 mM chloroauric acid (HAuCl4) with 50 mM sodium cholate.
I. Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Qiao et al. do not explicitly disclose that the sodium cholate is present in the amount of about 70-99 wt%. This deficiency is cured by the teachings of Qiao et al.
I. Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to employ the teachings of Qiao et al., outlined supra, to devise Applicant’s presently claimed particle.
Qiao et al. disclose a particle consisting essentially of a core of gold nanoparticles, and sodium cholate as a capping agent; wherein the particle is formed by reacting e.g. 1.0 mM chloroauric acid (HAuCl4) with 50 mM sodium cholate. Since Qiao et al. disclose that the reaction proceeds to completion, and that a higher amount of sodium cholate means a higher capping of the core of gold nanoparticles by sodium cholate, one of ordinary skill in the art would thus understand that the resulting particle, produced from a 3 mL solution comprising 1.0 mM chloroauric acid (HAuCl4) with 50 mM sodium cholate in which the reaction proceeds to completion, will thus contain about 5.91 mg of gold and 645 mg of sodium cholate. Hence, the total particle weight is about 651 mg, and sodium cholate is thus present in the amount of about 99 wt% of the particle.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
II. Claims 57 and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Qiao et al. (Langmuir. 2011; 27: 11090-11097), Hainfeld (U.S. Patent Application Pub. No. 2008/0089836), and Aziz et al. (U.S. Patent Application Pub No. 2017/0198216).
II. Applicant Claims
Applicant claims a microparticle comprising gold nanoparticles and sodium cholate; wherein the sodium cholate is present in the amount of about 70-99 wt%; and wherein the microparticle has a hexagonal prism shape with a diagonal length of 2.5-10 µm and a height of 2.5-6.5 µm.
II. Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Qiao et al. disclose a particle consisting essentially of a core of gold nanoparticles, and sodium cholate (i.e. a surfactant with a carboxylate functional group and a steroid moiety) as a capping agent; wherein the particle is formed by reacting e.g. 1.0 mM chloroauric acid (HAuCl4) with 50 mM sodium cholate.
Hainfeld discloses a microparticle comprising gold nanoparticles coated with multiple layers of surface binding molecules and amphiphatic molecules; wherein the surface binding molecule has e.g. a hydroxyl or carboxylate moiety and e.g. a steroid moiety; wherein the amphiphatic molecule can be e.g. sodium cholate; and wherein the microparticle is about 1-100 µm in size, or e.g. about 5 µm in size (see e.g. abstract; paragraphs 0014, 0016, 0017, 0023, 0038, 0051, 0082, 0160, 0163, 0164, 0242, 0244, 0245, 0272, 0301, 0303) .
Aziz et al. disclose a microparticle comprising a gold nanoparticle core covered with a capping agent, which capping agent is a surfactant with a carboxylate functional group; wherein the particle can have a hexagonal prism shape (see e.g. abstract; paragraphs 0014, 0071, 0080, 0094, 0111, 0112; example 7)
II. Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Qiao et al. do not explicitly disclose that the sodium cholate is present in the amount of about 70-99 wt%, and that the microparticle has a hexagonal prism shape with a diagonal length of 2.5-10 µm and a height of 2.5-6.5 µm. These deficiencies are cured by the teachings of Qiao et al., Hainfeld, and Aziz et al.
II. Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Qiao et al., Hainfeld, and Aziz et al., outlined supra, to devise Applicant’s presently claimed particle.
Qiao et al. disclose a particle consisting essentially of a core of gold nanoparticles, and sodium cholate as a capping agent; wherein the particle is formed by reacting e.g. 1.0 mM chloroauric acid (HAuCl4) with 50 mM sodium cholate. Since Qiao et al. disclose that the reaction proceeds to completion, and that a higher amount of sodium cholate means a higher capping of the core of gold nanoparticles by sodium cholate, one of ordinary skill in the art would thus understand that the resulting particle, produced from a 3 mL solution comprising 1.0 mM chloroauric acid (HAuCl4) with 50 mM sodium cholate in which the reaction proceeds to completion, will thus contain about 5.91 mg of gold and 645 mg of sodium cholate. Hence, the total particle weight is about 651 mg, and sodium cholate is thus present in the amount of about 99 wt% of the particle.
Moreover, since Hainfeld discloses that a gold nanoparticle can be coated with multiple layers of e.g. sodium cholate, and that the final product can be a microparticle about 1-100 µm in size, or e.g. about 5 µm in size, depending on e.g. factors that can be optimized in the reaction of chloroauric acid with the capping agent; and since Aziz et al. disclose that a microparticle comprising a gold nanoparticle core covered with a capping agent, which capping agent is a surfactant with a carboxylate functional group, can have a hexagonal prism shape, depending on e.g. the pH and other factors that can be optimized in the reaction of chloroauric acid with the capping agent; one of ordinary skill in the art would thus understand that the Qiao et al. method can be optimized as desired to achieve a microparticle with a hexagonal prism shape with a diagonal length of 2.5-10 µm and a height of 2.5-6.5 µm.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Potential Double Patenting Rejection
It is noted that co-pending U.S. Application No. 18/551,809 is directed to claims very similar to the present claims. However, it would appear that the claims of U.S. Patent Application No. 18/551,809 are directed to a composite particle comprising the compound with the steroid core structure and transition metal ions, which is substantially free of transition metal nanoparticles. The present claims are directed to a composite particle comprising the compound with the steroid core structure and transition metal nanoparticles. Hence, no double patenting rejection is being made at this time. However, depending on how claims get amended over the course of prosecution, a double patenting rejection may become necessary in the future.
Response to Arguments
Applicant's arguments filed November 24, 2025 have been fully considered but they are not found persuasive.
i) Applicant contends that “the fact that a reaction proceeds to completion does not mean that all of the starting materials are converted into the final product”; that “a chemistry textbook by Zumdahl…explains that the amount of product predicted by the theoretical yield is seldom obtained because of side reactions…and other complications”; that “Qiao merely states that its reaction proceeded to completion” and “a POSA would not have interpreted this to mean that all starting material ends up in the final product”; that the 37 CFR §1.132 Declaration of Dr. Omolola Eniola-Adefeso explains that one of ordinary skill in the art would have understood that capped metal nanoparticles “are made by a reduction reaction that uses a vast excess of the capping agent, which is then removed following completion of the reaction” and that “without any information regarding actual yield, a POSA in the art would have been unable to calculate the amount of sodium cholate in Qiao’s product based solely on Qiao’s reported theoretical yield”; that the Office’s calculations are “flawed as they assume that the reaction was conducted with stoichiometric quantities of the reactants, meaning that exactly the correct amounts so that all reactants run out at the same time”, i.e. “the limiting reactant is the reactant that is consumed first and that therefore limits the amounts of products that can be formed” and “it is not possible to know based on Qiao’s disclosure alone whether one of the reactants is limiting”; that “a detailed analysis as to the type of calculations a POSA could have made at the time the application was filed…would have estimated a theoretical maximum weight percent of cholate in Qiao’s particles of less than 3 wt%”; that “Qiao reports that all incorporated cholate will be at the surface of the AuNP, as would have been expected for standard AuNP fabrication at the time Qiao was published” and “capping agents are adsorbed to the surface and are not incorporated into the particle matrix”; that “Park…teaches on page 1918 that citrate molecules cover the surface of the AuNPs at ~2.8x10 -10 mol/cm2, but “as Dr. Eniola-Adefeso explains, the total mass of cholate as a capping agent at an equivalent packing density of citrate will overestimate the theoretical maximum weight percent of cholate in the AuNPs”, and that “even in the improbable event that Qiao’s particles had achieved a 100% surface coverage of cholate…Dr. Eniola-Adefeso describes how a POSA would have estimated that, even at a 100% coverage, the maximum weight percent of cholate in Qiao’s particles would have been 5.73 wt%”.
The Examiner, however, would like to point out the following:
1. First, is it acknowledged that Dr. Eniola-Adefeso is a distinguished expert in the art, and her testimony has been given substantial weight. The points Dr. Eniola-Adefeso has put forth are generally being treated as irrefutable facts. However, even in view of these facts in the case, the Examiner is not yet persuaded that the claimed subject matter represents a patentable advance in the art, for reasons explained below.
2. In view of Qiao, one of ordinary skill in the art could certainly, without question, arrive at a particle consisting essentially of a core of gold nanoparticles, and sodium cholate. One of ordinary skill in the art, in view of the express teachings of Qiao, would combine e.g. 1.0 mM chloroauric acid (HAuCl4) with 50 mM sodium cholate in a 3 mL solution, and let the reaction proceed for days, which reaction proceeds to completion. The reaction involves about 5.91 mg of gold and 645 mg of sodium cholate. Assuming all of the starting material ends up in the final product, it can be determined that the total particle weight is therefore about 651 mg, and sodium cholate is thus present in the amount of about 99 wt% of the particle. Indeed, it must be noted that Qiao never discloses that their product contains only 3 wt% of cholate, or 5.73 wt% of cholate. Qiao never states that cholate is employed in “vast excess” and that a large amount of the cholate is washed away and thus never ends up in the final product. Applicant simply has not proven, or even reasonably established, that Qiao’s final particle product does not, or cannot, contain 70-99 wt% cholate. Applicant has merely presented rather generic concerns and probabilities without properly establishing that any of the concerns or probabilities are actually applicable to the product of Qiao.
3. Regarding the chemistry textbook, and the notion of side reactions and other complications, it’s unclear what Applicant is alluding to in this specific case of Qiao. Indeed, as Qiao expressly states on page 11093, “there are only three starting materials, namely sodium cholate, HAuCl4, and water”, and Qiao discloses how they react to form the product. There are no side reactions or complications mentioned anywhere in Qiao. Applicant has not clarified by mentioning any particulars either.
4. The standard for determining patentability is in fact what would have been known or obvious to one of ordinary skill in the art at the time of filing the present application, not at the time Qiao was published. Many of Applicant’s arguments appear to be based on the premise of what would have been known to one of ordinary skill in the art at the time Qiao was published in 2011, not what was known to one of ordinary skill in the art at the time of filing the present application in 2022, with priority to a U.S. Provisional Patent Application in 2019.
5. Regarding the assertion that “the reduction reaction uses a vast excess of the capping agent”, this appears to be true for the reduction reaction itself. However, as explained in Qiao, the reduction reaction is but one step of their process. As noted by Qiao on page 11093, step 2 of their process is “Au(III) species are reduced into metallic Au by cholate and AuNPs are formed through a fast nucleation process”. Indeed, it would appear that there is a vast excess of cholate for this step. But that does not mean that all of the cholate is then simply washed away. On the contrary, Qiao teaches that cholate will cap onto the surface of AuNPs.
6. Regarding the assertion about “stoichiometric quantities” of reactants, such that “all reactants run out at the same time”, and the notion of “the limiting reactant being consumed first”, this appears to be another generic concept in chemistry merely thrown on the table with no explanation of how it is actually applicable in the present case to prove that Qiao’s final product does not or cannot contain 70-99 wt% cholate. Applicant is advised that cholate is not being consumed in the Qiao reaction. As Qiao explains, cholate’s hydroxyl groups serve to reduce Au(III) to Au to thus form the gold nanoparticle core of the product. Upon oxidation, the cholate has carboxylate groups that facilitate capping of the cholate onto the surface of the gold nanoparticle core. Hence, even after the Au(III) are all reduced to Au, no cholate has been consumed, and the cholate then proceeds to cap the surface of the gold nanoparticles.
7. Moreover, while Qiao was chiefly focused on the cholate that caps the surface of the gold nanoparticle core, one of ordinary skill in the art, at the time the present application was filed, would have understood that cholate can form multiple layers on the gold nanoparticle core. Indeed, cholate an amphiphilic, and while the cholate compounds that reacted with Au(III) to acquire carboxylate groups will then directly bind the gold nanoparticle core to thus form a layer of cholate, additional cholate, even cholate without carboxyl groups, can layer upon the cholate bound directly to the gold nanoparticle core via hydrophobic interactions (see, for example, the cited Hainfeld reference). Cholate is well known to form multilayer films and coatings and there is no reason why one of ordinary skill in the art, at the time of filing the present application, would not reasonably assume that all of the cholate employed in Qiao’s reaction would not layer upon the gold nanoparticle core, such that the final product contained 70-99 wt% cholate.
8. Regarding Park’s teaching that “citrate molecules cover the surface of the AuNPs at ~2.8x10 -10 mol/cm2”, it is noted that citrate and cholate have different properties. For example, while cholate is amphiphilic and can form micelles, citrate is hydrophilic and cannot form micelles on its own. Cholate can form multilayer films via hydrophobic interactions, but citrate cannot. Even if it could be concluded that cholate’s capping of the gold nanoparticle core by direct surface contact is similar to that of citrate, this does not mean that the final product with cholate is similar to the final product with citrate. Indeed, it can only be reasonably assumed that cholate will form multilayers via hydrophobic interactions, while citrate will not. It thus appears that all or most of the cholate present in the reaction medium will become part of the product, while all the citrate not capped directly to the gold core will get washed away.
9. Applicant’s theoretical calculations of the amount of cholate presumed in the final product of Qiao appear to be based on the premise that the only cholate in the final product is the cholate capped in direct contact with the gold nanoparticle core. But as just explained, this appears to be an oversimplification that ignores the fact that cholate can form multilayer coating on gold nanoparticle cores.
10. Therefore, in weighing the evidence of prima facie obviousness against Applicant’s arguments, the scales appear to tip in favor of the former at this time, for the reasons just discussed.
For the foregoing reasons, the 35 USC 103 rejections are hereby maintained.
Conclusion
No claims are allowed.
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/DAVID BROWE/Primary Examiner, Art Unit 1617