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 .
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.
Claims 1-26 are rejected under 35 U.S.C. 103 as being unpatentable over Bleiel WO 2016096931 A1 (Bleiel ‘931), in view of Bleiel et al. US 10,092,517 B2 (Bleiel ‘517).
Bleiel ‘931 teaches a cold-gelated mono-nuclear microencapsulates having a liquid core of GLP-1 release stimulating agent encapsulated within a gastro-resistant, ileal-sensitive, denatured protein membrane. The membrane protects the core material (i.e. native protein or disaccharide) during transit through the acidic environment of the stomach, preventing digestion of the active agent contained within the core, and releases the core material when it reaches the ileal environment. In addition, the use of a mono-nuclear core-shell type of encapsulate allows for a greater payload of core material (up to 92% of microencapsulate by weight) compared with the nonpareils of WO2009/053487 that deliver less than 5% of intact protein. In addition, as the microencapsulates of the invention are formed by cold gelation, food grade proteins of dairy or vegetable origin may be employed to generate the gastro-resistant, ileal-sensitive, membrane shell, thus obviating the need for specialized synthetic excipients such as EUDRAGIT. See page 8, lines 19-34. Membrane shell comprises denatured whey protein is found in pages 9, 11 and 13. Method for making the microcapsule is found in pages 12-14 and 22-. This protein membrane (which is made from thermally treated protein) has proven protection against harsh stomach acid and challenging proteolytic enzymes in the upper intestine. This unique delivery model generates micro-capsules with a gastro-resistant outer membrane that reacts to intestinal conditions and releases the core ingredient(s) at the proximal ileum, the systemic target site. Orally administering the microcapsule for use in a method of reducing blood sugar levels in a mammal is found in claim 21.
Bleiel ‘931 does not expressly teach core comprising insulin.
Bleiel ‘517 teaches a gelated microparticle suitable for delivery intact to the mammalian lower intestine via an oral route comprises a monodispersed matrix formed of at least partially hydrolyzed casein, chitosan, and an active agent. See Abstract. Solid oral dosage form including powder and compressed tablet is found in column 9. Active agent including insulin or an insulin analog is found in column 5, lines 55-62. Gelated microparticle having an average dimension of 10-250 microns is found in column 5, lines 65-67. Microparticle having water activity (Aw) of less than 0.20 is found in column 8, last paragraph.
Thus, it would have been prima facie obvious to one of ordinary skill in the art to optimize the teaching in Bleiel ‘931 to include active agent such as insulin in view of the teaching in Bleiel ‘517 to obtain a composition suitable for the delivery of active agent to the proximal ileum with the expectation to lower blood glucose level in a subject. This is because Bleiel ‘517 teaches delivering insulin in a gelated microparticle is known in the art.
Response to Arguments
Applicant's arguments filed 02/27/2026 have been fully considered but they are not persuasive.
Applicant argues that the microcapsules described in Bleiel II include at least partly hydrolyzed casein, chitosan, and a permeation enhancer. See the Abstract. This reference explicitly teaches the importance of chitosan for generating a synergistic effect on intestinal adhesion compared with gastric adhesion, and also teaches the importance of including a permeation enhancer to improve transport of an active agent across the intestinal mucosa. See the paragraph bridging columns 3 and 4. It follows that a skilled person in the art would not have expected success in delivering insulin to the ileum using the microcapsules of Bleiel I without also modifying the matrix of those microcapsules to incorporate chitosan or surfactant permeation enhancer, in view of the Bleiel II teaching that chitosan and surfactant permeation enhancer, excluded from the composition of claim 1, are required for improved intestinal adhesion and improved transport across intestinal mucosa.
However, Applicant’s arguments are not persuasive for the following reasons:
While Applicant amended the claims to exclude chitosan and/or surfactant, the Examiner is unable to determine the detrimental effect in a microcapsule taught in Bleiel I and Bleiel II. This is especially when the two references are directed to a microcapsule useful for the delivery of active agent to the ileal, and more specifically for the delivery of the claimed active agent, namely, insulin. Applicant has not provided comparison data showing detrimental effect and/or unexpected result in view of the present of chitosan.
For at least the above reasons, the rejection is maintained.
Conclusion
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSAN T TRAN whose telephone number is (571)272-0606. The examiner can normally be reached Monday-Friday, 8:30 am-5:30 pm.
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/SUSAN T TRAN/Primary Examiner, Art Unit 1615
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