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 .
Drawings
Figures 2A-2F of the drawings are objected to under 37 CFR 1.84 because they are presented in grayscale rather than solid black lines on a white background.
Drawings must be executed in durable black lines. Grayscale shading reduces the clarity of structural features (particularly the mesh structure, cavities, and expansion states shown in these figures) and does not comply with the formal requirements of 37 CFR 1.84. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
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.
Claim 14 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.
Claim 14 recites “a method of using the device…for the oral administration of the drug to a subject, the use comprising.” The claim mixes “method” and “use” terminology. It is unclear whether the claim is directed to a method comprising the recited steps or to a “use” of the device. See MPEP 2173.05(q).
Claim 14 further recites “releases the device in the small intestine,” “positions itself coaxially in the intestine,” and “migrates through the intestine epithelium.” It is unclear whether these structures are those of the previously recited subject. The claims should recast the preamble as a method and should identify the small intestine, intestine, and epithelium as those of the subject.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-3, 9-10, and 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Gross (US Publication No. 2010/0021536), hereinafter, Gross, in view of Curatolo (US Patent No. 5,443,843), hereinafter, Curatolo, and further in view of Zou (US Publication No. 2013/0172694), hereinafter, Zou.
Regarding claim 1, Gross discloses a swallowable, foldable and self-expandable oral drug delivery tubular device (ingestible capsule 20 configured for ingestion by a subject, para [0134-0135] and [0158]; outer surface 24 expands by stretching and/or unfolding in response to contact of the inner core or the outer surface with fluid in the small intestine, para [0136]; capsule 20 may be tube-shaped when swallowed, para [0030]; Figs. 1A-1B), the device:
comprising an outer peripheral surface (outer surface 24 expands by stretching and/or unfolding in response to contact of the inner core or the outer surface with fluid in the small intestine, para [0136]; Figs. 1A-1B);
having an expanded diameter of about 0.45 cm to about 6 cm (inner core 28 can expand such that its diameter is between 8 mm and 20 mm, para [0135]).
Gross fails, however, to disclose the device having an expanded length of about 2 cm to about 6 cm.
Curatolo teaches a device having an expanded length of about 2 cm to about 6 cm (Curatolo: for human use, the largest dimension of the orally administrable system in the expanded condition can vary from 2.5 to 6.0 cm, and preferably from 3.0 to 5.0 cm; col. 7, lines 7-20 and claim 8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the expandable tubular device of Gross to have an expanded length of about 2 cm to 6 cm, as taught by Curatolo, in order to ensure appropriate dimensioning for retention and contact within the human small intestine.
Modified Gross fails to disclose that the device comprises at least one cavity enclosing a drug, the at least one cavity facing outward from the outer peripheral surface of the device.
Zou teaches a device that comprises at least one cavity (Zou: drug reservoir 18 in Figs. 1-2, para) enclosing a drug (Zou: drug module 18 comprises a drug reservoir with a meshed side wall 12 which allows fluid from the environment to flow into and out of the drug reservoir; para [0017]), the at least one cavity facing outward from the outer peripheral surface of the device.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the expandable tubular device of modified Gross to include at least one outward-facing cavity enclosing a drug, as taught by Zou, in order to enable localized, high-concentration delivery of the drug directly to the intestinal wall.
Regarding claim 2, modified Gross discloses the device of claim 1, wherein the tubular device (capsule 20 may be tube-shaped when swallowed, para [0030]; Figs. 1A-1B) comprises a single tubular mesh (Zou: meshed side wall 12 which allows fluid from the environment to flow into and out of the drug reservoir in Figs. 1-2; para [0011], [0017] and claim 3).
Regarding claim 3, modified Gross discloses the device of claim 1, wherein the tubular device (capsule 20 may be tube-shaped when swallowed, para [0030]; Figs. 1A-1B) comprises foldable guiding members (arms 25 in Figs. 3A-3B) radially extending from a central tube or rod (arms 25 extend radially outward; para [0038] and [0141]), each foldable guiding member comprising a guiding member outer peripheral surface (outer surface of each of arms 25 in Figs. 3A-3B), the combined guiding member outer peripheral surfaces of all foldable guiding members forming the device's outer peripheral surface (the collective outer surfaces of expanded arms 25 for the peripheral contact surface of the device in Figs. 1A-1B).
Regarding claim 9, modified Gross discloses the device of claim 1, but fails to disclose that the device material comprises or consists of an elastomer.
Curatolo teaches that the device material comprises or consists of an elastomer (Curatolo: foldable retention arms that form the outer structure of the device can be made of elastomeric materials, including polysulfide elastomer and polyisoprene; col. 5, lines 40-64).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to form the device of modified Gross from an elastomer, as taught by Curatolo, in order to provide the flexibility and resilience needed for folding into a swallowable size and subsequent self-expansion in the intestine.
Regarding claim 10, modified Gross discloses an enteric capsule enclosing the device defined in claim 1 (coating 22 of capsule 20 comprises gelatin or another suitable material that dissolves when capsule 20 reaches the small intestine; para [0024] and [0135]).
Regarding claim 12, modified Gross discloses the device of claim 1, for oral administration of the drug to a subject (ingestible capsule 20 configured for ingestion by a subject, para [0134-0135] and [0158]).
Regarding claim 13, modified Gross discloses the device of capsule of claim 12, wherein the subject is a human (Curatolo: orally administrable system is for human use; col. 7, lines 12-13) and the device's expanded diameter is of about 1.1 cm to about 6 cm (inner core 28 can expand such that its diameter is between 8 mm and 20 mm, for example between 10 mm and 14 mm or between 12 and 15 mm; para [0135]).
Regarding claim 14, modified Gross discloses a method of using the device as defined in claim 1 enclosed in an enteric capsule (coating 22 of capsule 20 comprises gelatin or another suitable material that dissolves when capsule 20 reaches the small intestine; para [0024] and [0135]), for the oral administration of the drug to a subject (ingestible capsule 20 configured for ingestion by a subject, para [0134]), the use comprising:
orally administering the capsule to the subject (ingestible capsule 20 configured for ingestion by a subject, para [0134]), whereby when the capsule releases the device in the small intestine (coating 22 of capsule 20 comprises gelatin or another suitable material that dissolves when capsule 20 reaches the small intestine; para [0024] and [0135]), the device self-expands and positions itself coaxially in the intestine (outer surface 24 expands by stretching and/or unfolding in response to contact of the inner core or the outer surface with fluid in the small intestine providing 360 degrees of contact of the medication with the intestinal wall (coaxially) in Figs. 1A-1B, para [0042] and [0135-0136]), and
whereby the drug migrates through the intestine epithelium and enters systemic circulation of the subject (drug diffuses through epithelium; para [0047], [0087], [0136], and [0162]).
Regarding claim 15, modified Gross discloses the use of claim 14, wherein the subject is a human (Curatolo: orally administrable system is for human use; col. 7, lines 12-13).
Regarding claim 16, modified Gross discloses a capsule enclosing the device defined in claim 1, for oral administration of the drug to a subject (ingestible capsule 20 configured for ingestion by a subject, para [0134-0135] and [0158]).
Claims 4-7 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Gross in view of Curatolo and Zou, as applied to claim 1 above, and further in view of Bonner (US Publication No. 2018/0193621), hereinafter, Bonner.
Regarding claim 4, modified Gross discloses the device of claim 1, but fails to disclose that the drug is in a formulation further comprising at least one excipient.
Bonner teaches that the drug is in a formulation further comprising at least one excipient (Bonner: the capsule may contain, in addition to the device 100, permeation enhancers, enzyme inhibitors (e.g., protease inhibitors), mucus modifying agents, excipients, and the like, and combinations thereof; para [0120]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the drug formulation of modified Gross to further comprise at least one excipient, as taught by Bonner, in order to improve the stability, handling, or delivery characteristics of the active agent within the device.
Regarding claim 5, modified Gross discloses the device of claim 4, wherein the at least one excipient comprises a permeation enhancer (Bonner: the capsule may contain, in addition to the device 100, permeation enhancers, enzyme inhibitors (e.g., protease inhibitors), mucus modifying agents, excipients, and the like, and combinations thereof; para [0120]).
Regarding claim 6, modified Gross discloses the device of claim 4, wherein the at least one excipient comprises a protease inhibitor (Bonner: the capsule may contain, in addition to the device 100, permeation enhancers, enzyme inhibitors (e.g., protease inhibitors), mucus modifying agents, excipients, and the like, and combinations thereof; para [0120]).
Regarding claim 7, modified Gross discloses the device of claim 1, but fails to disclose that the drug has a molecular weight of about 1 kDa to about 50 kDa.
Bonner teaches that the drug has a molecular weight of about 1 kDa to about 50 kDa (Bonner: the reservoir 102 comprises at least one agent selected from molecules having a molecular weight of at least 1,000 Da... 2,000 Da… 5,000 Da… 10,000 Da… 50,000 Da… the agent will typically have a molecular weight less than about 20,000 Da; para [0059]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the expandable tubular device of modified Gross to select a drug having a molecular weight of about 1 kDa to about 50 kDa, as taught by Bonner, in order to deliver macromolecular therapeutics that benefit from localized intestinal delivery.
Regarding claim 11, modified Gross discloses the capsule of claim 10, but fails to disclose that the capsule further comprises a filler.
Bonner teaches that the capsule further comprises a filler (Bonner: the capsule may contain, in addition to the device 100, permeation enhancers, enzyme inhibitors (e.g., protease inhibitors), mucus modifying agents, excipients, and the like, and combinations thereof, para [0120]; fillers or extenders, para [0159]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the expandable tubular device of modified Gross to include a filler in the enteric capsule, as taught by Bonner, in order to occupy space, improve handling, or aid in the proper positioning and release of the device within the capsule.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Gross in view of Curatolo and Zou, as applied to claim 1 above, and further in view of (Nielsen, Line Hagner, Stephan Sylvest Keller, and Anja Boisen. "Microfabricated devices for oral drug delivery." Lab on a Chip 18.16 (2018): 2348-2358.), hereinafter, Nielsen.
Regarding claim 8, modified Gross discloses the device of claim 1, but modified Gross fails, however, to disclose that device comprises drug cavities having a volume between 10 nL and 100 µL.
Nielsen teaches drug cavities having a volume between 10 nL and 100 µL (Nielsen: teaches microcontainer reservoir volumes of 10 nL; page 2350, col. 2, para 1, Fig. 2B).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the drug cavities of modified Gross to have a volume between 10 nL and 100 µL, as taught by Nielsen, in order to provide a controlled, discrete dose of drug suitable for localized delivery from micro-scale reservoirs.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARIAH K WHITROCK whose telephone number is (571) 272-3534. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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/ZACHARIAH K WHITROCK/Patent Examiner, Art Unit 3783
/WESLEY G HARRIS/Examiner, Art Unit 3783
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