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 .
Election/Restrictions
Applicant’s election of the species: free fatty acid “oleic acid” and active ingredient “hydrocortisone” in the reply filed on 3/24/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Status
Claims 7-13 and 17-19 are cancelled.
Claims 20-28 are new.
Claims 1-6, 14-16 and 20-28 are pending.
Priority
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Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 10/12/23, 11/03/23, 01/29/25, 02/17/25, 04/7/25 and 04/11/25 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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 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.
Claims 1-6, 14-16 and 20-27 are rejected under 35 U.S.C. 103 as being unpatentable over Patel et al. (US6309663; hereinafter Patel’663) and Patel et al. (US6294192; hereinafter Patel’192).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims, for example:
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Claim interpretation: The specification defines “substantially free of TAGs as 5% or less TAGs [0096, 00178], which would reasonably include 0%.
Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a drug delivery research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from emulsion drug delivery with core knowledge of lipid chemistry and oil selection, droplet size analysis, surface chemistry, emulsion electrostatics, solubilization techniques including self-microemulsifying drug delivery systems (SMEDDS)1, bioavailability and excipient selection— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1, 14-16, 20-21, 23 and 25-27, Patel’663 teaches triglyceride free compositions (Title; claim 1) for improved drug delivery (Column 1, lines 5-10) where the drug can be corticosteroids (Claim 112) in the form of a solution, emulsion, cream, lotion or gel (Claims 64, 141) where upon mixing with an aqueous diluent the average particle size is less than about 100 nm (Claim 126) or less than about 50 nm (Claim 127), which appears to read on the claimed Z average size of about 300 nm or less. How the size is measured is not relevant to the examination of a composition of matter claim. Patel’663 teach mixtures of ionizable surfactant oleic acid (C18:1), linoleic acid (C18:2), caprylic acid (C10) and capric acid (C10) and ricinoleic acid (Claims 19 and 20-21; column 24, 1.19 Ionizable Surfactants) and teaches at least two surfactants including oleic and linoleic acid in an amount greater than 10% by weight (Claim 34). Patel’663 teach that among the specifically preferred hydrophobic surfactants are oleic acid, glyceryl monolaurate, glyceryl monooleate, glyceryl monocaprylate (Column 26, lines 63-67; claim 108). Thus, Patel’663 teaches a composition comprising a monoacylglycerol oil dispersed in a liquid with an average particle size less than 300 nm that is substantially free of triacylglycerols and comprising two or more different fatty acids oleic and linoleic acids. Patel’663 teach a typical composition with 10-100% absorption enhance composition; 0-10% enzyme inhibitor active; 0-60% solubilizer; 0-50 mM bufferant; 0-20% hydrophilic polymer and 0-50% other additives (Column 53, line 65 through column 54, line 7).
Patel’663 teaches oleic acid and linoleic acid as absorption enhancing agents that should be present at least about 10% by weight, preferably at least about 20% (Column 35, lines 23-47).
Regarding claim 3, the oil dispersed in a liquid composition of Patel’663 does not appear to include any exogenous additive with thickening or crystallization inhibiting properties that is not naturally present in the oil in an amount sufficient to thicken the composition or inhibit crystallization formation, respectively. In fact, Pate’663 teaches that viscomodulators can be further added (Claim 42) thus indicating their absence in the independent claim.
Regarding claims 1, 2, 14-16 and 26, Patel’192 teaches triglyceride free compositions (Title; abstract; claims 1-3) comprising the corticosteroid (Claim 38) hydrocortisone (Column 24, line 2) as well as hydrophobic surfactants oleic acid (Claim 29), glyceryl monocaprate, glyceryl monocaprylate, glyceryl monolaurate and glyceryl monooleate (Claim 30) with an average particle size of less than about 50 nm (Claim 31). Patel’192 teaches: “Surprisingly, the present inventors have found that compositions including a combination of a hydrophilic surfactant and a hydrophobic surfactant can solubilize therapeutically effective amounts of hydrophobic therapeutic agents without recourse to the use of triglycerides, thereby avoiding the lipolysis dependence and other disadvantages of conventional formulations.” (Column 4, lines 53-60). Patel’192 teaches: “The choice of specific hydrophobic and hydrophilic surfactants should be made keeping in mind the particular hydrophobic therapeutic agent to be used in the composition” (Column 6, lines 1-4).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Patel’663 is that Patel’663 do not expressly teach wherein the oil composition comprises monoacylglycerols (MAGs) in an amount from about 50% to about 80% by weight of the total weight of the oil composition with two or more fatty acids with hydrocortisone as the active ingredient and wherein the composition does not include any exogenous additive with surfactant and/or emulsifier properties that is not naturally present in the oil in an amount sufficient to enhance droplet stability. This deficiency in Patel’663 is cured by the teachings of Patel’192. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the composition of Patel’663 wherein the composition does not include any exogenous additive with surfactant and/or emulsifier properties that is not naturally present in the oil in an amount sufficient to enhance droplet stability and comprises monoacylglycerols (MAGs) in an amount from about 50% to about 80% by weight of the total weight of the oil composition with two or more fatty acids with hydrocortisone as the active ingredient, as suggested by Patel’192, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because Patel’663 do teach a typical composition with 10-100% absorption enhancing composition, which comprises the monoacylglycerol(s) and at least two hydrophobic ionizable surfactant fatty acids such as oleic acid and linoleic acid. Consequently, it is then merely routine optimization to obtain a composition substantially free of triglycerides with about 50-80% monoacylglycerol(s) and a combination of oleic and linoleic acids with a reasonable expectation of success. Patel’663 suggest a corticosteroid as the active ingredient and Patel’192 name hydrocortisone. It is then merely judicious selection of known corticosteroids such as hydrocortisone for use in the pharmaceutical system of Patel’663 with a reasonable expectation of success.
Furthermore, Patel’192 teaches that the hydrophilic surfactant assists in the solubilization of the therapeutic agent and not to enhance droplet stability. Thus, no exogenous additive with surfactant and/or emulsifier properties that is not naturally present in the oil in an amount sufficient to enhance droplet stability are present. Active ingredient solubility is enhanced; not droplet stability.
The difference between the instant application and Patel’663 as modified by Patel’192 is that Patel’663 as modified by Patel’192 do not expressly teach an average zeta potential of less than -30 mV or a polydispersity index of less than 0.3 and wherein the Z average size of the particles does not change by more than 15% over 28 days when stored at room temperature. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the composition of Patel’663 wherein the composition an average zeta potential of less than -30 mV or a polydispersity index of less than 0.3 and wherein the Z average size of the particles does not change by more than 15% over 28 days when stored at room temperature. The disperse particles of Patel’663 inherently have some average zeta potential and some polydispersity index and some degree of stability. A low PDI would indicate a uniform and narrow size distribution, where such consistency would be desirable for drug delivery. A negative zeta potential would be indicative and expected from the presence of free fatty acids. Thus, an average zeta potential of less than -30 mV and a polydispersity index of less than 0.3 appear normal for such systems. Patel’663 also comment that the compositions are stable upon storage (Column 50, lines 33-37) and so the limitation of the particles does not change by more than 15% over 28 days when stored at room temperature appears to be implicit in the same materials employed by Patel’663 or optimized by the ordinary artisan to extend the shelf life with a reasonable expectation of success.
The difference between the instant application and Patel’663 as modified by Patel’192 is that Patel’663 as modified by Patel’192 do not expressly teach wherein the two or more different fatty acids comprise Cl 8: 1 in an amount from about 25% to about 50% out of the total fatty acid content, Cl8:2 in an amount from about 25% to about 55% out of the total fatty acid content of the oil; wherein the two or more fatty acids comprise C18:1 in an amount from about 15% to about 50% out of the total fatty acid content, and Cl8:2 in an amount from about 20% to about 60% out of the total fatty acid content of the oil; wherein the two or more different fatty acids comprise C8:0 in an amount from about 50% to about 65% out of the total fatty acid content of the oil and C10 in an amount from about 35% to about 50% out of the total fatty acid content of the oil; wherein the two or more different fatty acids comprise Cl 8:1 in an amount from about 25% to about 50% out of the total fatty acid content, Cl8:2 in an amount from about 25% to about 55% out of the total fatty acid content of the oil; wherein the two or more different fatty acids comprise C8:0 in an amount from about 50% to about 65% out of the total fatty acid content of the oil and C10 in an amount from about 35% to about 50% out of the total fatty acid content of the oil; wherein the two or more fatty acids comprise Cl8:1 in an amount from about 15% to about 50% out of the total fatty acid content, and Cl8:2 in an amount from about 20% to about 60% out of the total fatty acid content of the oil; and wherein the two or more fatty acids comprise Cl8:1 in an amount from about 15% to about 50% out of the total fatty acid content, and Cl8:2 in an amount from about 20% to about 60% out of the total fatty acid content of the oil.
However, as noted above, Patel’663 teaches mixtures of ionizable surfactant oleic acid (C18:1), linoleic acid (C18:2), caprylic acid (C10) and capric acid (C10) (Claims 19 and 20-21; column 24, 1.19 Ionizable Surfactants) and teaches at least two surfactants including oleic and linoleic acid in an amount greater than 10% by weight (Claim 34). It then appears to be nothing more than judicious selection of the named oleic acid (C18:1), linoleic acid (C18:2), caprylic acid (C10) and capric acid (C10) for use in the pharmaceutical system and optimization of the amount to use. Patel’663 establishes the general conditions and components to employ. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Consequently, without more the limitations of claims 20-25 and 27 appears obvious.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Patel et al. (US6309663; hereinafter Patel’663) as evidenced by Wikipedia Castor Oil ([online] retrieved on 5/19/26 from: https://en.wikipedia.org/wiki/Castor_oil; 2 pages).
Applicant claims:
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Regarding claim 28, Patel’663 teaches triglyceride free compositions (Title; claim 1) for improved drug delivery (Column 1, lines 5-10) where the drug can be corticosteroids (Claim 112) in the form of a gel (Claims 64, 141). Patel’663 teach mixtures of ionizable surfactant oleic acid (C18:1), linoleic acid (C18:2), caprylic acid (C10) and capric acid (C10) and ricinoleic acid (Claims 19 and 20-21; column 24, 1.19 Ionizable Surfactants) and teaches at least two surfactants including oleic and linoleic acid in an amount greater than 10% by weight (Claim 34). Patel’663 teach that among the specifically preferred hydrophobic surfactants are oleic acid, glyceryl monolaurate, glyceryl monooleate, glyceryl monocaprylate (Column 26, lines 63-67; claim 108). Patel’663 teach a typical composition with 10-100% absorption enhance composition; 0-10% enzyme inhibitor active; 0-60% solubilizer; 0-50 mM bufferant; 0-20% hydrophilic polymer and 0-50% other additives (Column 53, line 65 through column 54, line 7). Patel’663 teaches oleic acid and linoleic acid as absorption enhancing agents that should be present at least about 10% by weight, preferably at least about 20% (Column 35, lines 23-47). Patel’663 suggests a gel formulation (Claim 64; column 41, lines 44-54) and an oil composition comprising ricinoleic acid (Claim 19) and the monoacylglycerols where specifically preferred hydrophobic surfactants are glyceryl monolaurate, glyceryl monooleate, glyceryl monocaprylate (Column 26, lines 63-67; claim 108) in the composition thereby providing a first component gel and a second component oil composition comprising a monoacylglycerol and a fatty acid in the castor oil fatty acid profile. As evidenced by Wikipedia Castor Oil, 85-90% of the fatty acids in castor oil is ricinoleic acid, with under 10% of each of the other fatty acids. Thus, 10% below those amounts is equivalent to 0% of the other fatty acids in the fatty acid profile of castor oil.
Patel’663 do not expressly teach wherein the oil composition comprises monoacylglycerols (MAGs) in an amount from about 50% to about 80% by weight of the total weight of the oil composition and the oil composition comprises a fatty acid profile comprising each fatty acid found in castor oil and comprising amounts of each fatty acid that is within 10% above or below of that found in castor oil. However, Patel’663 do teach a typical composition with 10-100% absorption enhancing composition, which comprises the monoacylglycerol(s) and hydrophobic ionizable surfactant fatty acid ricinoleic acid. Consequently, it is then merely routine optimization to obtain a composition substantially free of triglycerides with about 50-80% monoacylglycerol(s) and a ricinoleic fatty acid profile within 10% of the fatty acid ricinoleic acid found in castor oil and 0% of the other fatty acids found in castor oil with a reasonable expectation of success.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined 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 combined references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 See for example Akula et al. (Hindawi Publishing Corporation International Scholarly Research Notices Volume 2014, Article ID 964051, 11 pages).
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