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
The Applicant’s reply filed on 4/28/26 is acknowledged. Claims 1-12 and 15-20 are pending. Claims 12 and 15-20 have been withdrawn. Claim 9 have been amended. Claims 1-11 are under consideration.
Rejections Withdrawn
The rejection of Claim 9 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the amended claim.
Rejections Maintained and New Grounds of Rejections
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 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Myung et al. (Macromolecular Research, 2008; cited in IDS) in view of Dyakonov et al. (Journal of Drug Delivery, 2012).
Myung et al. teach the fabrication of silk fibroin nanoparticles (e.g. abstract). Myung et al. teach a method comprising:
adding an aqueous solution containing a silk fibroin (i.e. natural polymers) to cyclohexane (i.e. organic solvent) and Triton X-100 (i.e. nonionic surfactant), and homogenizing a resulting mixed solution to generate a natural polymer colloidal suspension; and
adding the natural polymer colloidal suspension to a mixture of methanol and ethanol (i.e. an alcohol) (e.g. page 605 “Formation of Silk Fibroin Nanoparticles”).
Myung et al. teach that the methanol has dual functions in this process, the removal of the microemulsions and the dehydration of the silk to induce its assembly into a crystalline form (e.g. page 606 “results and Discussion” and Figure 1). Myung et al. do not teach that the alcohol has 3 to 4 carbon atoms, or an alcohol recited in claims 2 and 3. This is made up for by the teachings of Dyakonov et al.
Dyakonov et al. teach a platform for controlled drug delivery based on silk fibroin (SF) and to explore the feasibility of using SF in oral drug delivery (e.g. abstract). Dyakonov et al. studied the effect of dehydrating solvents (methanol, ethanol, and isopropyl alcohol) on formation of β-sheets and concluded that isopropyl alcohol treatment gave good crystalizing effect (e.g. page 4 Section 3.2, Table 3).
Regarding Claims 1-4 and 7-10, it would have been obvious to one of ordinary skill in the art at the time of filing to replace the methanol and ethanol of Myung et al. with the isopropanol of Dyakonov et al. It would have been obvious to one of ordinary skill in the art to combine the elements as claimed by known methods with no change in their respective functions, and the combination yielding nothing more than predictable results. One of ordinary skill in the art would have predicted success as both Myung and Dyakonov are directed to silk fibroin particles comprising methods utilizing alcohol dehydration agents and one of ordinary skill would have been motivated in order to provide the benefits of good crystalizing effect as taught by Dyakonov et al. Simple substitution of one known element for another to obtain predictable results is obvious.
Regarding Claims 5 and 6, Myung et al. teach that the aqueous silk fibroin solution was prepared by dissolving cocoons of Bombyx mori (e.g. abstract and “Experimental”).
Regarding Claim 11, Myung et al. teach that fluorescent molecule Rhodamine B was encapsulated in the silk fibroin nanoparticles (e.g. page 606 “results and Discussion” and Figure 1).
Response to Arguments
Applicant's arguments filed 4/28/26 have been fully considered but they are not persuasive.
Applicant argues beginning on page 6 that a person of ordinary skill in the art reading Myung et al. would have concluded that use of methanol is important to Myung's process, and would not be motivated to replace it with another alcohol, including isopropanol, because removing the methanol would render the modified process unsatisfactory for its intended purpose of using the dual function of methanol to remove microemulsions and dehydrate the silk.
This is not found persuasive. As described supra, while Myung et al. used the alcohols methanol and ethanol, they do not disparage the use or inclusion of other alcohols. Myung et al. do not appear to have tested isopropyl alcohol. Myung et al. teach that methanol has dual functions in this process, the removal of the microemulsions and the dehydration of the silk to induce its assembly into a crystalline form. Similarly, Dyakonov et al. teach that isopropyl alcohol treatment also gives good crystallizing effect in addition to being a dehydrating solvent (e.g. Section 3.2). It would have been obvious to one of ordinary skill in the art at the time of filing to replace the methanol and ethanol of Myung et al. with the isopropanol of Dyakonov et al. in order to provide the benefits of good crystalizing effect as taught by Dyakonov et al. Simple substitution of one known element for another to obtain predictable results is obvious. “When a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Applicant further argues that Dyakonov discloses that the use of isopropyl alcohol promotes good crystallization of fibroin; however, this relates to the release of the drug from the fibroin (superior drug release occurs when p-sheet formation is good) and is not related to the smoothness or size of the fibroin microspheres. Applicant continues that the size of the microspheres prepared by Dyakonov is 26.05 + 1.92 µm (page 7, left column, first para), much larger than Myung's nanoparticles, which are less than 1 µm.
This is not found persuasive. First, Myung et al. also teach the use of the polymers for drug delivery (e.g. page 604). Second, the prior art need not have the same reason for combining or modification as applicant. It is noted that the instant claims do not require a smoothness, size, or any outcome from following the method steps other than “a method for producing natural polymer microspheres”. 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).
Applicant further argues that the present Application provides technical solutions to the problem of producing natural polymer microspheres, particularly silk microspheres having a particle diameter on a micrometer scale (e.g., about 2 to 20 pm) and a smooth surface shape. Applicant further argues that the fibroin microspheres obtained by the method disclosed in Myung results in silk microspheres which had a rough surface and some that did not retain their spherical shape.
This is not found persuasive. As above, the instant claims do not require a smoothness, size, or any outcome from following the method steps other than “a method for producing natural polymer microspheres. Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Conclusion
No claim is allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLE PLOURDE BABSON whose telephone number is (571)272-3055. The examiner can normally be reached M-Th 8-4:30; F 8-12:30.
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/NICOLE P BABSON/ Primary Examiner, Art Unit 1619
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