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 .
Response to Amendment
Applicant’s response of 07/13/2026 has been received and entered into the application file. Claims 64-72, 75, 77, and 79-83 are pending in this application.
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.
Claims 64-65 are rejected under 35 U.S.C. 103 as being unpatentable over Becher (DE 19849848 A1 translated, 2000), Krumme (US 2008/0241216 A1), Nielsen et al. (Microfabricated devices for oral drug delivery, Lab Chip, 2018), and Jeong et al. (Viscoelastic lithography for fabricating self-organizing soft micro-honeycomb structures with ultra-high aspect ratios, nature communications, 2016).
Becher discloses orally administrable therapeutic dosage form comprising a covering in the form of a capsule to prevent premature dissolution on the way from the oral cavity via the esophagus into the stomach (claim 1). The covering is a capsule made of gelatinous polymer (claim 2). The covering can consist of water-soluble film-forming polymers, such as hydroxypropyl methylcellulose (HPMC) (claim 4). The material contained in the capsule is a sheet-shaped, active-substance containing structure made of film-forming polymer and is present in the casing as a roll or folded body (claim 6). The film forming polymer can have hydrophobic and hydrophilic parts (hydrophobic at low pH and hydrophilic at higher pH) ([0010]). Becher provides drawings of such invention (Fig 1a-1c).
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Becher does not disclose dimensions of the rolled foil.
Krumme discloses a preparation containing active and/or auxiliary substances for the time- and/or dose-controllable release of said substances, comprising at least two layers in rolled or folded shape (Abstract). The rolled-up or folded preparations are embedded in the form of hard or soft gelatin capsules ([0041]). When the spirally wound up preparation is exposed to a body fluid, the active substance-containing adhesive dissolved and partially unrolls the system ([0028]). The sheet-like form can have a winding core with diameter of 0.5 to 30 mm ([0034]). At least one layer is pressure-sensitive adhesive; the width of said layer may vary along its extension in longitudinal direction. The result of this is so-called width profile ([0026]). Thickness of a layer is in the range of between 1 µm to 500 µm ([0037]). The rolled or folded sheet is characterized in that at least one of the parameters thickness, width and concentration of the layer can be varied, not constant ([0018]). The preparation can be delivered to intestines ([0042]). Suitable active agents include vitamins, analgesics, sympathomimetics, and many other agents ([0044]). The rolled-up preparation unrolls, which active substances can enter from the layer into the body fluid in correspondence with the surface area which has been disposed at a given moment. The release profile can be controlled by the geometry of the active substance layer, speed of unrolling, and layer geometry ([0051]).
Nielsen discloses microfabricated devices for oral drug delivery (Abstract). Another hypothesis is that these microfabricated devices can protect drugs until they reach their final destination of delivery. It is anticipated that the unidirectional release as well as a sustained resident time due to mucus attachment or penetration will allow more drug to be absorbed. Indeed, the transfer of drug across an intestinal epithelial cell monolayer has been seen to increase by a factor of ten using such microdevices (pg 2348). Nielsen discloses design, microfabrication technologies and materials for oral drug delivery devices (Table 1).
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Above references do not teach plurality of adjacent, contiguous compartments.
Jeong discloses that micro- and nano-structures have been used for the production of a variety of applications. Jeong discloses that the shapes and sizes of the honeycomb structure can be easily modulated. The honeycomb structure is used to prepare a drug delivery patch (Abstract). Jeong discloses that the PDMS structures of honeycomb structure displayed an excellent capacity for drug or cell loading (pg 2).
From Krumme, one of ordinary skill in the art would immediately envisage that the dimensions of rolled foils and unrolling speed would determine the characteristics of a rolled foil composition. Furthermore, the unrolling mechanism of rolled foils would inherently have radial pressure. This practice would be routinely practiced by one of ordinary skill in the art to optimize such compositions.
Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined teachings of Becher and Krumme to arrive at a rolled foil composition comprising an active agent on the foil with specific diameters fit to deliver such compositions to intestines. Nielsen and Jeong disclose that microdevices with honeycomb structures are routinely used to deliver drugs. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Regarding claim 65, the rolled foil which specific diameter, width, and thickness can be routinely optimized by one of ordinary skill in the art as discussed above.
Claims 66-72, 75, 77, and 79-83 are rejected under 35 U.S.C. 103 as being unpatentable over Becher (DE 19849848 A1 translated, 2000), Krumme (US 2008/0241216 A1) Nielsen et al. (Microfabricated devices for oral drug delivery, Lab Chip, 2018), and Jeong et al. (Viscoelastic lithography for fabricating self-organizing soft micro-honeycomb structures with ultra-high aspect ratios, nature communications, 2016) as applied to claims 64-65 above, and further in view of Yu et al. (Stimuli-responsive delivery of therapeutics for diabetes treatment, Bioengineering & Translational Medicine, 2016) and Abramson et al. (A luminal unfolding microneedle injector for oral delivery of macromolecules, Nat Med, 2019).
Yu emphasizes the importance of diabetic therapeutics, insulin and glucagon-like peptide 1. However, conventional treatments based on subcutaneous injections are often associated with poor glucose control and poor patient compliance. The pH-responsive systems for oral drug delivery are a promising way to deliver insulin (Abstract). Oral delivery is considered the most patient-friendly method for insulin administration. However, the low pH of gastric medium in the stomach and various enzymes in the GI tract may degrade insulin. Peppas and coworkers pioneered the utilization of pH-responsive complexation gel for oral delivery of insulin. They demonstrated that the insulin was absorbed in the upper small intestine (pg 324). Enteric capsules or enteric coatings are utilized to improve the drug efficiency by protecting insulin from the digestive enzymes. Mitragotri and coworkers loaded mucoadhesive intestinal patches in an enteric capsule for oral insulin delivery. The capsule could protect insulin-loaded patches in the acidic environment of the stomach, while release them in the intestine. The released patches adhered to the intestinal mucosal layer to promote insulin absorption. Recently, they further loaded the intestinal devices with a permeation enhancer into a capsule coated with a pH-responsive enteric coating to improve oral absorption of insulin (pg 325). Apart from polymeric materials, inorganic nanoparticles have also been explored as insulin carriers due to their high loading capacity and good compatibility with insulin. Sun et al. utilized mesoporous silica NPs to increase the loading capacity of insulin (pg 325).
Abramson discloses an ingestible capsule with unfolding microneedle injector which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms (Abstract).
Yu teaches that there are ongoing efforts to deliver insulin orally with good efficacy. Abram discloses a capsule with unfolding microneedle injector arms for delivery of macromolecules. Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to envisage the delivery of insulin using a capsule containing insulin-loaded patches and/or rolled foils as discussed above. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Regarding claim 67, insulin within a capsule is discussed above.
Regarding claim 68, a gelatin capsule and an enteric coating is discussed above.
Regarding claim 69, one of ordinary skill in the art knows that stomach’s pH is 1.0-3.7 and the duodenum and jejunum’s pH is 6.0-7.0 (See Figure 2 of Yu). One of ordinary skill in the art would also know what the pH value of the enteric coating needs to be.
Regarding claim 70, Krumme discloses that the component of the base material of layers containing active substance may be polymers including silicone polymers, rubber ([0045]). Any of the polymers mentioned by Krumme ([0045]) would ideally support elastic deformation since the rolled foil is a preferable feature of the invention. Additionally, Yu discloses the advantage of mesoporous silica as a delivery vehicle for insulin as discussed above. Nielsen discloses that PDMS is routinely used to provide the necessary elastic force, and to create a drug delivery device.
Regarding claim 71, radial pressure is discussed above. The unrolling mechanism of rolled foils would inherently have some kind of radial pressure depending on the rolled foil diameters and speed of unrolling as discussed above.
Regarding claim 72, Krumme discloses that the foil can comprise two regions – one configured as active substance-containing, water-soluble adhesive, and another region water-insoluble sealing region ([0056]). Likewise, one of ordinary skill in the art would freely modify parts of the surface of the foil to be water soluble or insoluble.
Regarding claim 75, Abramson discloses that each of the device’s three degradable arms propelled a dissolving drug-loaded microneedle patch into the tissue wall (pg 3, Engineering the Device). Hexagonal shape is disclosed by Jeong as discussed above.
Regarding claim 77, active ingredients on the rolled foil is discussed above.
Regarding claim 79, Krumme discloses that the unwound length of the total system may advantageously be in the range of between 5 mm and 300 mm ([0038]). However, the length of the unwound foil could vary through routine experimentation. One of ordinary skill in the art would immediately envisage that the dimensions of rolled foils and unrolling speed would determine the characteristics of a rolled foil composition.
Regarding claims 80-81, Krumme describes a planar, helical, rolled-up administration form comprising two layers; the outward-facing layer being an active substance-free film which is soluble in water ([0007]). This layer when exposed to a body fluid, erodes or dissolves and consequently exposes active substance-containing matrix material ([0007]). Krumme discloses an eroding layer which initially protects the active substance-containing matrix. Similarly, the sealing layer protects the active substance until the dosage form reaches the site of action. Additionally, Abramson discloses that dosage forms are often coated with an enteric polymer using a spray coat process (pg 18).
Regarding claim 82, Krumme discloses a process of manufacturing the preparation (claim 20). Furthermore, one of ordinary skill in the art would consider any and all shapes of ridges as taught by Nielsen and Jeong. Nielsen discloses micropatches (single and multi-compartment) and Jeong discloses hexagons are routinely used to deliver drugs.
Regarding claim 83, one of ordinary skill in the art would be familiar with a method of administering a pharmaceutical composition. Abramson discloses that specialized LUMI devices were administered (orally) to the swine to determine the capsule actuation time (pg 14). Whether to gather experimental data or, to provide therapeutic relief, an oral dosage form would be taken orally in a subject.
Response to Arguments
Applicant’s arguments filed 07/13/2026 have been fully considered but is not found to be persuasive.
On pages 6-7 of remarks, applicant explains that claim 64 is directed to a single, continuous rolled foil whose convex surface bears interconnected ridges. On page 8 of remarks, applicant argues that Krumme’s “spirally wound up preparation” unroll when exposed to body fluid; unrolling is driven by dissolution of an adhesive layer. However, Becher discloses that the dosage form is a sheet-shaped, active ingredient-containing structure made of polymer and is present in the casing as a roll or folded body ([0018]). One of ordinary skill in the art would expect the folded body to unfold at the site where the casing was ruptured. Additionally, Nielsen discloses that a self-folding microdevice was placed on a piece of inclined pig intestine then the microdevice was inspected the for the depth of engulfment in the mucosa (pg 2355, left col, 2nd paragraph). One of ordinary skill in the art would immediately envisage that a self-folded or a folded microdevice in the intestine would apply some sort of pressure when unrolled in an intestine. On page 8, applicant argues that claim 64 requires “convex surface comprises interconnected ridges defining a plurality of adjacent, contiguous compartments”. This limitation was taught by Jeong as previous discussed in the Non-Final mailed on 04/13/2026 – the honeycomb structure is taught by Jeong and also shown in the drawings of instant application submitted on 09/27/2022. The Examiner cannot determine why the structure of the instant application and the radial pressure from the action of unrolling would be any different from prior art references.
On pages 8-9, applicant argues that Jeong is directed to a fabrication method only. However, Jeong discloses that advanced micro- and nano-scale technologies have enabled broad applications of these structures, even in the biomedical fields of drug delivery. Effective drug or cell delivery applications and tissue engineering techniques require structures that can pack a high number of cells or drugs as compactly as possible (pg 2, left col, 1st paragraph). Likewise, one of ordinary skill in the art would consider any and all structures for delivering drugs for these microdevices – including rolled foils. Jeong discloses that soft micro-honeycomb structures prepared from PDMS was fabricated; the PDMS structures displayed an excellent capacity for drug or cell loading (pg 1, left 1, 2nd paragraph). Per MPEP 2145 (IV), One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references.
On page 9, applicant continues to argue that Nielsen and Jeong do not teach modifying a rolled intestinal foil to include the claimed compartments. Nielsen discloses that microdevices are routinely used to deliver drugs such as insulin (See Table 2). These microdevices are also situated on intestinal cell membrane and the active ingredient is then released (See Fig. 1). Nielsen discloses microdevices for oral drug delivery, and does not explicitly have to mention the specific word “rolled foil”. One of ordinary skill in the art would certainly consider any and all oral formulations using these microdevices.
On page 10, applicant argues that not all unrolling polymer structure satisfies the claimed limitation with respect to radial pressure. The instant specification only shows fabrication of PDMS foil. No other foils were fabricated to show that the PDMS foil had an unexpectedly superior property of exerting radial pressure. Applicant claims that material properties, thickness, length, and relationship to the diameter of the designated intestine all impart this claimed radial pressure. However, none of these features are commensurate in scope in claim 64. Claim 64 is a rolled foil with a convex surface (housing honeycomb pattern), inside a covering layer (capsule), and the length is at least half a length of an inner circumference of the designated intestine. No material property, thickness, length can be found in claim 64.
On page 11, applicant continues to attack references individually and argues impermissible hindsight. Per MPEP 2145 (X) (A), "[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper." The references relied upon by the examiner are all related to delivering drugs using microdevices such as a rolled foil.
One of ordinary skill in the art would routinely experiment with a rolled foil with compartments wherein the compartments would contain a drug. These rolled microdevices would routinely be optimized to deliver drugs within the target site such as the intestine.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN SEUNGJAI KWON whose telephone number is (571)272-7737. The examiner can normally be reached Mon - Fri 8:00 - 5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached at 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOHN SEUNGJAI KWON/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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