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
Status of Application
1. Applicants’ arguments/remarks filed 15 July 2026 are acknowledged. Claims 1-2, 4, 7-10, 13, 15, 18-20, and 33-35 are currently pending. Claims 3, 5-6, 11-12, 14, 16-17, and 21-32 are cancelled. Claims 2, 4, 7, 8, 10, and 15 are amended. Claims 33-35 are newly added. Claims 1-2, 4, 7-10, 13, 15, 18-20, and 33-35 are examined on the merits within.
Withdrawn Objections/Rejections
2. Applicants’ arguments, filed 15 July 2026, with respect to the claim objections have been fully considered and are persuasive. The objections of claims 2, 4, and 7 have been withdrawn. The 35 U.S.C. 112(b) Rejections of claims 4, 8, 10, and 15 have been withdrawn in view of the claim amendments.
Maintained Objections/Rejections
Claim Objections
3. Claim 1 is again objected to because of the following informalities: the claim recites “an aqueous lipid nanocarrier formulation”, “the lipid nanocarrier formulation” and “the lipid aqueous nanocarrier formulation”. For consistency purposes, each reiteration of “an aqueous lipid nanocarrier formulation” should recite “the aqueous lipid nanocarrier formulation.” Appropriate correction is required. Claims 18 and 19 are included in this objection for the same deficiencies.
Claim Rejections – 35 U.S.C. 112(b)
4. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claim 9 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
6. Claims 9 recite “% weight of the formulation”. Does this phrase refer to the aqueous lipid nanocarrier formulation or the dosage form? Clarification is requested.
Claim Rejections – 35 U.S.C. 103
7. 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.
8. Claim(s) 1-2, 4, 7-10, 13, 15, 18-20, and 33-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rizwan et al. (Journal of Pharmaceutical Sciences, 2009) in view of Nielsen et al. (European Journal of Pharmaceutics and Biopharmaceutics, 2017).
Rizwan et al. teach swelling and phase behavior of phytantriol and glyceryl monooleate matrices with varying water loadings. See abstract. The bicontinuous cubic phase, referred to as cubic phase or Q is a promising delivery system for low molecular weight drugs, proteins, peptides, amino acids, and nucleic acids. See page 4191. Samples contain FITC-Ova. See page 4194. At 20% or higher water content the phase is cubic, while water contents of 20% and 25% result in reverse hexagonal phase. See Table 1. The release of the incorporated active is thought to be controlled partly by the unique microstructure, where the active has to diffuse through the structure to access the external solution. The pore size and tortuosity of the water channels and the stiffness and high viscosity of the cubic phase contributes to the sustained release of the entrapped active. See page 4192.
Rizwan et al. do not teach an enteric coating.
Nielsen et al. teach cubosomes encapsulating model antigen ovalbumin via spray drying and their potential application in oral vaccine delivery. See abstract. Cubosomes were prepared with glyceryl monooleate (i.e., monoolein). See page 14, Section 2.2. The cubosome powders are filled in microcontainers and spray coated with Eudragit S100. See page 15.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to add an enteric coating to the formulation to control the location of delivery of the active agent to increase therapeutic effectiveness. One would have been motivated, with a reasonable expectation of success, because Nielsen et al. teach the importance of pH dependent coatings, such as Eudragit S100, to control the location of release within the body. It would have been well within the purview of the skilled artisan to modify the amounts of long chain lipids and water to control the phase of the liquid crystalline structure which in turn affects the effectiveness of the drug delivery system. It would have been well within the purview of the skilled artisan to control the pore size to control the entrapment and release of active ingredients for therapeutic effectiveness. It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to incorporate the formulation of Rizwan et al. into a capsule because Nielsen et al. teach the effective encapsulation of glyceryl monooleate cubosomes in microcontainers coated with a pH dependent coating for oral delivery. It would have been well within the purview of the skilled artisan to substitute one type of therapeutic agent for another to yield predictable results because Rizwan teaches drugs, proteins, peptides, amino acids, and nucleic acids as therapeutic agents effectively delivered.
Response to Arguments
Applicants’ arguments filed 15 July 2026 have been fully considered but they are not persuasive.
9. Applicants argued, “Rizwan does not teach that the phases can aid in the delivery and improved bioavailability of physiologically labile therapeutic agents. The prior art teaches away from aqueous formulation to be used as a delivery system for therapeutic agents. Nielson comprises dispersed particulate mesophase rather than a non-dispersed bulk mesophase. The cubosomes of Nielsen are spray dried. Nielsen does not provide in vivo studies, providing little evidence it would work. Example 1 shows green fluorescent protein and insulin can be delivered to rats with a similar efficacy compared to subcutaneous injection. Example 3 shows both HCFX and HCH can be delivered orally with similar efficacy compared to subcutaneous injection. There is insufficient motivation to combine Rizwan with Nielsen. Nielsen does not address the technical problem. Rizwan and Nielsen do not provide an enabling disclosure.”
In response to applicants’ arguments, the examples provide a specific active agent, a specific lipid, a specific enteric coating, and specific amounts of each ingredient resulting in a specific ratio of therapeutic to lipid. However, claim 1 is much broader as being directed to any therapeutic agent combined with any lipid and enterically coated. The claim does not include amounts or ratios. Thus a side by side analysis cannot be conducted regarding the examples and their effects compared to the instant claims. The claims do not mention “phases can aid in the delivery and improved bioavailability of physiologically labile therapeutic agents”. Rizwan teaches bicontinuous cubic phase, referred to as cubic phase or Q, is a promising delivery system for low molecular weight drugs, proteins, peptides, amino acids, and nucleic acids. Thus the prior art acknowledged the effects for delivery. The prior art of Nielsen was provided to make obvious the use of an enteric coating. The water content having no effect on the release of ovalbumin is not a teaching away but instead shows no effect on therapeutic release. Rizwan teaches the lipid and therapeutic as instantly claimed and Nielsen makes obvious coating with an enteric material. With regards to an enabling disclosure, the prior art does not have to exemplify each and every embodiment. The Examiner must take the prior art for what it teaches and, in the instant case, the prior art makes obvious an aqueous lipid nanocarrier formulation comprising a therapeutic and enteric coating.
Thus this rejection is maintained.
Conclusion
10. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, 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 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.
Correspondence
11. No claims are allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA WORSHAM whose telephone number is (571)270-7434. The examiner can normally be reached Monday-Friday (8-5).
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/JESSICA WORSHAM/Primary Examiner, Art Unit 1615
