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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4 May 2026 has been entered.
Status of the Claims
Claims 1, 2, 4-6, and 8-10 are pending, presented for examination, and rejected as set forth in greater detail below.
Claim Interpretation
Applicants claims are directed to a method of forming a nanodispersion by mixing fat soluble compounds with food grade lipids at a temperature falling within a defined range. This combination is then homogenized with surfactants, the resulting emulsion which is then subjected to ultrasonication under specified conditions or high pressure homogenization to reduce the particle size of the emulsion. This emulsion is then to be combined with shell or coating materials and spray dried. Claims 2 and 3 place particular limitations on the particle size and polydispersity of the composition obtained. Claim 4 specifies the lipid to be used, Claim 5 the surfactant, and Claim 6 the shell/coating materials. Claim 7 indicates the method is to be used to encapsulate fat-soluble compounds, with Claim 8 providing a Markush-type listing of specific fat-soluble compounds to be encapsulated.
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.
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, 2, 4-6, and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Parikh (U.S. 5,922,355), in view of Dorly Del Curto (WO02/051390), Tonge (WO2008/065451), and Domb (WO2021/214764).
Parikh describes submicron size particles of water-insoluble substances combining surface modifiers such as poloxamers and phospholipids that are stable and resistant to particle size growth, as well as means of their production. (Abs.; Col.1, L.7-19). Nutrients are among the variety of water-insoluble agents suitable for such methods. (Col.2, L.52-61). A variety of phospholipids, addressing the lipid limitations of Claims 1 and 5, are recited as suitable for use in these methods and compositions. (Col.2, L.65 – Col.3, L.5). Parikh indicates that additional surface modifiers find favorable use in these compositions and methods, and include each of the casein and acacia of Claims 1 and 6, as well as the sorbitan esters, polyethylene glycol esters, and polyoxypropylene/polyoxyethylene copolymers (recited by Parikh as “poloxamers”), of Claims 1 and 5. (Col.3, L.6-49). Parikh indicates that by adhering to the surface of the particles, maintenance of particle size and increasing stability of these compositions is achieved. (Col.3, L. 50-63). Parikh indicates that any of a variety of processes can be used in obtaining these compositions, with an exemplary embodiment involving homogenization at controlled temperature followed by high-shear sonication to reduce particle sizes to the range of 300-500nm. (Col.4-5, “Example 1”).
Dorly Del Curto also describes the formation of lipid nanoparticles to be used to formulate dosage forms of poorly water-soluble substances, more specifically any of a variety of proteins. (Pg.1, L.5-7; Pg.2, L.8-15). Employing monoglycerides as a lipid matrix, more specifically those having a melting point of at least 70°C, allows the sparingly soluble agents like proteins to be distributed through the matrix. (Pg.3-4). Each of the phospholipids, sphingolipids, polyoxypropylene-polyoxyethylene copolymers of the Parikh disclosure as well as the instant claims are recited as usefully stabilizing surfactants. (Pg.4). Dorly Del Curto indicates the drug is to be incorporated into the lipid matrix employing the well-known co-melting technique, whereby a lipid is melted at a temperature in advance of the melting point of that lipid, to which the drug, and any additional excipients such as the surfactants, can be added. (Pg.8-9). Combined with the teaching that the lipid should have a melting point in excess of 70°C, this suggests a range of melting temperatures overlapping, and therefore rendering obvious, that of Claim 1. See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (“A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.”). These components are mixed to homogeneity, then subjected to high pressure homogenization to reduce particle size. (Pg.9).
Tonge also describes processes of forming lipid nanoparticles wherein an active compound is dissolved, solubilized, or dispersed within a melted lipid which is then combined with solutions of surfactants and additives to provide for lipid nanoparticles. (Pg.3). Tonge indicates that a variety of vitamins serve as water-insoluble active agents in such formulations and methods. (Pg.35). Tonge indicates that advantageously, these particles possess a PDI of less than 0.4. (Pg.30, L.31-32).
Domb also describes methods of forming lipid nanoparticles containing active agents where the lipids are heated to provide for the homogeneous distribution of active and surfactant through the lipid matrix, which is used to obtain a dispersion with uniformity of particles. (Pg.13-14). Domb indicates that spray-drying is a means recognized for isolating such active-loaded nanoparticles to provide a free-flowing powder for further use. (Pg.14).
So the art at the time the instant application was filed described methods of providing lipid nanoparticles whereby a lipid matrix such as a phospholipid is heated to a temperature above the melting point of the lipid, for example 70°C, to incorporate and distribute a fat soluble active, such as a vitamin, throughout the lipid. The art additionally teaches combining these lipid solutions with compositions of any of a variety of surfactants including sorbitan or polyoxyethylene esters, or poloxamers, which are then homogenized and downsized to provide nanoparticles of lipid, fat soluble active, and surfactants possessing a PDI of less than 0.4. The art additionally indicates that surface coating of these nanoparticles with additives including each of the acacia and casein serves to stabilize the nanoparticles so formulated by reducing agglomeration of the particles.
It must be remembered that “[w]hen 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 at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to have followed a method whereby a lipid matrix such as a phospholipid is heated to a temperature above the melting point of the lipid, for example 70°C, to incorporate and distribute a fat soluble active, such as a vitamin, throughout the lipid, then combine these lipid solutions with compositions of any of a variety of surfactants including sorbitan or polyoxyethylene esters, or poloxamers, which are then homogenized and downsized to provide uniform sized nanoparticles of lipid, fat soluble active, and surfactants possessing a PDI of less than 0.4, which are then surface coated with stability-enhancing additives including either acacia or casein to arrive at methods “yielding no more than one would expect from such an arrangement.”
Response to Arguments
Applicant's arguments filed 4 May 2026 have been fully considered.
Applicants repeat their arguments concerning the use of a solvent in one embodiment of the methods described by Dorly Del Curto. Applicants argument once again ignores the fact that the “solvent stripping” technique the Examiner assumes applicants refer to is, in fact, taught as an alternative to the “well-known co-melting technique” the Examiner has relied on, but also newly ignores the fact that the language forming the basis of applicants argument is no longer found in the claims. See Dorly Del Curto (Pg. 8, L.30 – pg.9, L.4)(“Said peptide and/or protein is incorporated into lipid matrices by well-known co-melting technique…[t]he drug can also be incorporated into the lipid matrix using the “solvent-stripping” technique.”). Applicants repeated assertion that there would have been no reasonable expectation of success in utilizing a technique the Examiner has not suggested a skilled artisan would rely on is no more persuasive now than it was when originally presented.
Applicants next recap various embodiments of teachings provided by each of the Parikh, Dorly Del Carlo, Tongue, and Domb references, stating that various claim elements that the Examiner has not asserted can be found in each are, in fact, absent from the particular reference. This approach, treating each reference piecemeal rather than pausing to consider what the combined teachings of the references provide the skilled artisan when considered as a whole is improper. This is because it has long been known that 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, 426 (C.C.P.A. 1981) (citing Application of Young, 403 F.2d 754, 757 (C.C.P.A. 1968) (indicating that "[O]ne cannot show non-obviousness by attacking references individually where ... the rejections are based on combinations of references").
Applicants assertion that the specific combination of monoglycerides, surfactants, and shell materials provide unexpected advantages is unsupported by objective evidence and therefore unpersuasive, as the Declaration referred to in Applicants response cannot be found of record. Once more, 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). “[A]ppellants have the burden of explaining the data…they proffer as evidence of non-obviousness.” Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). The evidence relied upon should establish “that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance.” Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). This evidence is absent.
Concerning applicants bullet points listed as section “F” of the response:
Dorly Del Curto does not require organic solvents, nor are organic solvents excluded from the methods of the instant claims per the amendments applicants filed 4 May 2026;
Commercial utility is not a secondary indicia of nonobviousness: in fact, utility is a statutory requirement of a patentable invention (See 35 U.S.C. 101);
Regulatory advantage, also, is not a secondary indicia of nonobviousness;
Nor is reproducibility a secondary indicia of nonobviousness, as the enablement of the methods of the invention is also a statutory requirement (See 35 U.S.C. 112(a)).
Finally, applicants are reminded that the sonication energy input range newly added to the claims is recited as an alternative to the high pressure homogenization step also recited by the claims, and which has been taught by Dorly Del Curto as a means of downsizing an emulsion to reduce its particle size since 2002.
For at least these reasons, applicants arguments are unpersuasive.
Conclusion
No Claims are allowable.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN M BASQUILL whose telephone number is (571)270-5862. The examiner can normally be reached Monday through Thursday, 5:30 AM to 4 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571) 272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
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