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 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 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. The Examiner notes that while the preamble of these methods claimed refer to the process as one which is “solvent-free,” by the actual steps recited by the process claimed nothing is particularly excluded. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004) ("[L]ike the term ‘comprising,’ the terms ‘containing’ and ‘mixture’ are open-ended."). Invitrogen Corp. v. Biocrest Manufacturing, L.P., 327 F.3d 1364, 1368, 66 USPQ2d 1631, 1634 (Fed. Cir. 2003) ("The transition ‘comprising’ in a method claim indicates that the claim is open-ended and allows for additional steps."); Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997) ("Comprising" is a term of art used in claim language which means that the named elements are essential, but other elements may be added and still form a construct within the scope of the claim.). Furthermore, review of applicants disclosure as originally filed clearly indicates that at least in the penultimate coating step, solvents are employed. See Paragraph [0031] (“7. To 100 mL of the mixture, add 20g maltodextrin, 5g of sodium caseinate and 50mL of distilled water.”). Owing to the conflict in claim terminology, and the lack of description of a solvent-free process in the disclosure as originally filed, this preamble language is being interpreted as a descriptive name of the set of limitations defining the claimed method. IMS Tech., Inc. v. Haas Automation, Inc., 206 F.3d 1422, 1434-35 (Fed. Cir. 2000)(indicating that claim language has no separate limiting effect if, for example, “the language merely gives a descriptive name to the set of limitations in the body of the claim that completely set forth the invention.”). 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 17 December 2025 have been fully considered.
Applicants amendments to the claims have addressed the indefiniteness of Claims 3, 4, and 6 by eliminating the conflict between a specific PDI and the more generic recitation of “high uniformity,” or of reciting generic classes of components as well as specific species falling within the breadth of those genera.
The rejection of Claims 3, 4, and 6 as indefinite under 35 USC 112(b) has therefore been WITHDRAWN.
Applicants amendments to Claims 7 and 8 have addressed the issue of these claims failing to further limit the subject matter of Claim 1.
The rejection of Claims 7 and 8 under 35 USC 112(d) has been WITHDRAWN.
Applicants arguments concerning the examiner’s interpretation of the claims, more particularly the impact of the preamble phrase “solvent free” have been fully considered and are unpersuasive. As set forth previously, the skilled artisan would understand that in the absence of a limiting definition, anything recognized by the art as a solvent would be excluded from the process steps recited. See “Water, the Universal Solvent” available at https://www.usgs.gov/water-science-school/science/water-universal-solvent (9 June 2018). Nothing of the actual process steps recited exclude any solvents whatsoever, so the interpretation of the preamble as simply giving a descriptive name to the set of limitations in the body of the claim that completely set forth the invention remains valid.
Applicants next recite the limitations of the amended claims and state, without evidence or supporting discussion, that Parikh does not teach this invention. This pattern of response is legally insufficient to rebut a prima facie case of obviousness. See In re Lovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011) (“[T]he Board reasonably interpreted Rule 41.37 to require more substantive arguments in an appeal brief than a mere recitation of the claim elements and a naked assertion that the corresponding elements were not found in the prior art.”). Applicants assertion that Parikh fails to disclose controlling PDI to 0.4 or below is unpersuasive, as the Examiner has not asserted it does. Applicants are reminded that all elements of each prior art reference need not read on the claimed invention, rather, the proper test for obviousness is what the combined teachings would have suggested to a person of ordinary skill in the art. In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000).
Applicants arguments concerning the use of a solvent in one embodiment of the method of Dorly Del Curto 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.” 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 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 unpersuasive.
Applicants arguments concerning Tonge and Domb assert that neither of these references teach or suggest limitations which the Examiner has not asserted are taught by either of these references. Applicants arguments concerning the Tonge and Domb references are unpersuasive for this reason.
Applicants arguments concerning the unexpected ability of the “inventive” process to provide for a PDI less than 0.4 is unpersuasive, as Tonge describes providing lipid nanoparticles with a polydispersity index of less than 0.4.
Applicants assertion that the specific combination of monoglycerides, surfactants, and shell materials provide unexpected advantages is unsupported by objective evidence and therefore unpersuasive. This is because 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).
For at least these reasons, applicants arguments are unpersuasive.
Conclusion
No Claims are allowable.
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.
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.
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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