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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8/10/2026 has been entered.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-23 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao, Y., et al., (Sci. Rep., 2016), cited previously, in view of Mendes, J.B.E., et al., (Sci. World J., 2012), cited previously as evidenced by Shah, S., et al., (J. Photochem Photobiol B, 2017), cited previously, in view of Feczko et al. "Comparison of the preparation of PLGA–BSA nano- and microparticles by PVA, poloxamer and PVP",Colloids and Surfaces A: Physicochemical and Engineering Aspects, Volume 319, Issues 1–3, 15 April 2008, Pages 188-195. This modified rejection was necessitated by amendment.
Zhao teaches methods of making resveratrol containing polyester polymer nanoparticles comprising the steps of dissolving the polymer (PLGA) in a first solvent (dichloromethane) and resveratrol (second emulsifier) in a second solvent (ethanol) along with doxorubicin (therapeutic/biologically active agent) and then emulsifying this solution with PVA (first emulsifier) in water and drying to form particles. See entire disclosure, especially page 3, paragraph 7. Regarding claims 22-23, the solution of PVA in water of Zhao reads on applicant’s “second aqueous phase comprising the first emulsifier” as a broadest reasonable interpretation of the claims includes wherein the first and second aqueous phase may be the same chemical composition.
Regarding the limitation on the ratio of 1st to 2nd solvent in the organic phase, Zhao is silent with respect to a ratio in the claimed range. However, the preparation of emulsion compositions having variable amounts of solvents in each phase is within the level of skill of one having ordinary skill in the art at the time of the invention. It has also been held that the mere selection of proportions and ranges is not patentable absent a showing of criticality. See In re Russell, 439 F.2d 1228 169 USPQ 426 (CCPA 1971).
Zhao does not teach modifying the ratio of resveratrol in the compositions nor its effects on the particles.
Mendes teaches methods of making polyester polymer particles comprising the steps of mixing the polymers PHBV/PCL in the first and second solvents chloroform and methylene chloride and emulsifying the organic phase into an aqueous phase with PVA, drying to form particles, and modifying the amount of resveratrol in the compositions. See page 2, paragraph 6 and table 1. Mendes teaches that the particles have a smooth surface at low concentrations of resveratrol in PCL and a rough surface when high levels of resveratrol are used solidifying it on the surface and providing for a burst release of the drug as well as changes the size of the particles, drug loading, and the drug encapsulation efficiency. See figure 2, page 5, paragraph 6, and table 3. Mendes teaches changing the concentration from 0-0.4 g/40 mL organic phase or 0-10 mg/mL, the data point of 10 mg/mL is within the claimed range. See table 1.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to modify the amount of the drug resveratrol in the PLGA nanoparticles in order to adjust the release rate, drug loading, encapsulation efficiency, and morphology of the particles in order to control the drug release from the particles. One of ordinary skill in the art at the time of the invention would have had a predictable expectation of success in making this combination as the prior art already encapsulates resveratrol and other drugs in PLGA nanoparticles using emulsification and Mendes teaches that you can control the drug loading and release as well as particle morphology by altering the drug loading in the particles.
Zhao and Shah do not state that doxorubicin is a detectable label.
Shah provides evidence that doxorubicin is fluorescent and can provide for information on changes in the local environment which is useful when synthesizing nano-particles for doxorubicin entrapment. See abstract.
Zhao while teaching use of PVA emulsifier is silent with respect to a specific molecular weight for the emulsifier.
Feczko is used for its teaching on emulsifiers such as PLGA (MW 8,000) and PVA (MW includes data point of 30,000) were well known at the time of the claimed invention to be useful in emulsion techniques to form particles. See entire disclosure, especially abstract and page 189 left col 2nd full ¶.
Since Zhao already teaches use of polymer emulsifiers one of ordinary skill would have a high expectation of success of using emulsifiers within the claimed molecular weight range such as those of Feczko with predictable results. Obviousness stems from the notion that Zhao already teaches the genus of the emulsifiers claimed and Feczko teaches the use of PLGA and PVA within the recited weight range. The artisan would recognize that, based on the disclosure of Zhao that numerous emulsifiers, including PLGA and PVA within the recited weight range could be substituted into the composition with similar results. Thus the claimed invention would have been prima facie obvious since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
Response to Arguments
Applicant's arguments filed 8/10/2026 have been fully considered but they are not persuasive.
Applicants assert neither Zhao or Mendes teaches modifying the amount of second emulsifier to control particle topology.
As noted in the previous action and again above, Mendes teaches that the particles have a smooth surface at low concentrations of resveratrol (2nd emulsifier) in PCL and a rough surface when high levels of resveratrol are used. The functional limitation of controlling topology by controlling the amount of second emulsifier is therefore disclosed in Mendes.
Applicants pick on Zhao for exemplifying amounts of resveratrol below the claimed amounts.
The examples within Zhao were given solely for the purpose of illustration and were not to be construed as being limiting to their invention since many variations are possible without departing from the spirit and scope of the invention. Adjusting the amounts of emulsifier in this composition is considered obvious until criticality can be shown. Regardless Mendes provides good reason to adjust resveratrol and was used for this teaching and does teach amounts within the claimed range.
Applicants assert Mendes teaches microparticles not nanoparticles and the examiner mischaracterized the reference.
The relevance of the size of the particle in this reference is unclear as it pertains to the claims. The claims are drawn to a method of making particles and are silent with respect to nano or micro-particles. Thus, the relevance of this assertion is very unclear as the claims don’t even feature a limitation that the particles are nanosized. Even if they did the secondary reference Mendez is simply not used for particle size.
Applicants assert Mendez uses a single solvent for each of two polymer systems and does not teach the claimed two-solvent system.
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). Clearly Mendes was not used for teaching the claimed two solvent system which is covered in the primary reference.
Applicants assert the exemplified PHBV particles of Mendes are rough at every loading and therefore cannot be the product of Resveratrol. Applicants further assert the PCL particles were smooth at ever loading. Applicants assert these results do not suggest modifying the concentration of second emulsifier would alter the topology of the particle.
Mendes clearly teaches modifying the amount of the drug resveratrol in the PLGA nanoparticles in order to adjust the release rate, drug loading, encapsulation efficiency, and morphology of the particles in order to control the drug release from the particles. Simply because applicants can pick and choose some specific examples over a narrow range where different loading of resveratrol did not produce different topologies is not convincing in view of its clear teaching on the effects of resveratrol amounts of the particles.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES W ROGERS whose telephone number is (571)272-7838. The examiner can normally be reached 9:30-6:00 PM.
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/JAMES W ROGERS/Primary Examiner, Art Unit 1618
