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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 15, 2025 has been entered.
Response to Amendment
This office action is responsive to the amendment filed on July 15, 2025. As directed by the amendment: claims 789, 795, 806, 812, 814 and 816-817 have been amended, claims 1-788, 811, 813 and 815 have been cancelled, and no claims have been added. Thus, claims 789-810, 812, 814 and 816-819 are presently pending in this application.
Response to Arguments
Applicant’s arguments, see Remarks, filed July 15, 2025, with respect to the rejections of newly amended independent claims 789, 806 and 814 under 35 U.S.C. §103 have been fully considered and are persuasive. Therefore, the rejections have been withdrawn. However, upon further consideration, a new grounds of rejection is made in view of Aran et al. (Aran) US 2017/0246438 A1.
On pages 8-9 of the Remarks, Applicant argues that P0269 describes the gas cylinder containing gas at an elevated pressure, and that this conveys to one of ordinary skill that the pre-pressurized compressed gas container embodiments may have pressures as claimed. Applicant further argues that nothing in the specification at P0654 suggests the claimed range is limited to any specific embodiments. In response, Examiner notes that P0654 teaches the claimed range for some, but not all embodiments. Therefore, it may also be true that the claimed ranges do not apply to all embodiments.
On pages 9-10, Applicant argues that the pressures taught by Aran are too low to penetrate the epithelial layer, with support from Applicant test data. In response, Examiner notes that Applicant’s test data is not directly relevant since Aran’s devices were not tested. Furthermore, Aran issued as patent 10,729,895 and MPEP 1701 recites every patent is presumed to be valid.
On page 11 of the Remarks, Applicant argues that Houzego does not disclose any pressure parameters necessary for trans-epithelial delivery. In response, Applicant notes that Aran teaches trans-epithelial delivery, and Houzego is applied to teach use of an alternative pressure source, namely the use of pre-pressurized compressed gas as a pressure source in P0078. Please note that Houzego also teaches the pressure source of Aran in P0077. Also see Houzego P0074-0083, teaching alternative pressure sources.
On page 11 of the Remarks, Applicant argues that although Trovato teaches a canister for storing compressed gas as claimed, the pressure of the of gas it stores is at a higher pressure than claimed, and that additionally it is for a different purpose which is to inflate a balloon, rather than to drive a piston. In response, Examiner agrees with Applicant’s characterization of Trovato’s teachings, but also notes that Trovato is applied solely for teaching a cannister capable of containing a high pressure compressed gas. Trovato not only teaches that the canister can hold a high pressure, but also that it is designed for use within an orally administered ingestible device.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 789-810, 812, 814 and 816-819 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Here, independent claims 789, 806 and 814 recite that the compressed gas provides a fluid pressure of about 100 psig to about 500 psig. As noted above in the Response to Arguments, explicit support for these claim limitations in relation the embodiment being claimed are not in the written description. Claims depending from independent claims 789, 806 and 814 are rejected at least because they depend from claims 789, 806 and 814.
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 789-801, 806-810, 812, 814, 816-819 are rejected under 35 U.S.C. 103 as being unpatentable over Aran et al. (Aran) US 2017/0246438 A1 in view of Houzego et al. (Houzego) US 2002/0055734 A1 in view of Trovato et al. (Trovato) US 2008/0194912 A1.
Regarding claim 789, Aran discloses a method of treating a patient (P0101-0102 and shown in Figs. 1A-D) comprising: orally administering an ingestible device containing a dispensable substance to the patient (ingestible device 100 is administered to a subject orally, P0101); the dispensable substance (active agent solution, P0101) comprising a therapeutically effective amount (P0088) of a pharmaceutical (P0084-0088); releasing compressed gas (CO2, P0101); the released compressed gas contacting and acting on a piston (piston 103, P0101); and the piston moving and ejecting the dispensable substance from the ingestible device (the increase in pressure exerts a force on the piston 103, which moves the piston 103 into the active agent reservoir 102 and the active agent solution is then ejected from the nozzle 104 with high velocity, P0101) in the gastrointestinal tract of the patient (intestinal site, P0101) as at least one jet (active agent solution is ejected from the nozzle 104 with high velocity, P0101).
Aran P0083 teaches use of active agents with molecular weights between 5 kDa to 100 KDa, but does not explicitly teach the molecular weight of the active agent within the P0101 embodiment of Aran.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the embodiment of P0101 of Aran with a pharmaceutical within the claimed molecular weight range of about 3 kDa to about 200 kDa since Aran teaches use of active agents within that range for the purpose of diagnosis, treatment, or prevention of a disease or as a component of a medication, Aran P0079.
Aran teaches delivering active agent through the mucosal layer and to the underlying tissues in P0054, wherein the underlying tissues of the mucosa include the submucosa as shown in Applicant’s Fig. 1A. However, with regard the embodiment of P0101, Aran does not explicitly teach providing delivery of the dispensable substance to the submucosa.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the P0101 embodiment of Aran for trans-epithelial delivery of the dispensable substance to the submucosa of the gastrointestinal tract of the patient as taught by Aran P0054 for the purpose of submucosal delivery, wherein delivery to the submucosa may be controlled by the amount of chemicals inside the power reservoir P0104, such that the device can be configured to eject the active agent at a pressure and velocity sufficient to deliver through a mucosal layer P0054 and P0065.
Aran does not teach the compressed gas as pre-pressurized.
However, Houzego teaches an ingestible device wherein pre-pressurized gas (compressed nitrogen or air, P0078) is used as an energy source for expelling a drug, P0075.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of Aran with pre-pressurized gas as taught by Houzego as a simple substitution of one known method of generating pressure to dispense substance from an ingestible capsule for another to obtain predictable results, see MPEP 2143(B). Aran contained a method which differed from the claimed method by the substitution of a pre-pressurized compressed gas for a power reservoir that generated compressed gas from a chemical reaction. Pre-pressurized compressed gas and their function to displace a substance from an ingestible capsule are well known in the art as evidenced by Houzego. One of ordinary skill in the art could have substituted one know element (method for dispensing a substance from an ingestible device by generating compressed gas with a chemical reaction as taught by Aran) for another (method for dispensing a substance from an ingestible device by a pre-pressurized gas as taught by Houzego) and results of the substitution would have been predictable, that is the compressed gas is used for dispensing a substance from the ingestible device.
Houzego teaches use of a pre-pressurized gas, but does not explicitly teach the pre-pressurized gas stored in a container.
However, Trovato teaches an ingestible capsule having a pre-pressurized compressed gas container (see P0188 wherein the gas pressurizing module 1602 is a cannister for storing a compressed gas).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to combine the compressed gas of Houzego with the cannister of Trovato for the purpose of storing compressed gas.
Aran in view of Houzego in view of Trovato does not teach the compressed gas providing a fluid pressure of about 100 psig to about 500 psig on the dispensable substance.
Aran teaches that the devices may be configured to produce various amounts of pressure to propel the active agent formulation out the device with sufficient velocity to penetrate a desired layer of tissue, including power sufficient for transmucosal delivery, P0055. Therefore, pressure exerted is disclosed to be a result effective variable in that changing the amount of pressure affects the velocity of active agent propelled from the device which affects the depth below the tissue surface of delivery of active agent formulation. Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato wherein the compressed gas provides a fluid pressure of about 100 psig to about 500 psig on the dispensable substance since it has been held that “where 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).
Regarding claim 790, Aran in view of Houzego in view of Trovato teaches the method of claim 789 wherein the ingestible device is configured to directly deliver the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing systemic uptake of the pharmaceutical that is at least about 15% relative to intravenous or subcutaneous administration of an equal amount of the pharmaceutical (the ingestible device of Aran in view of Houzego in view of Trovato is fully capable of directly delivering the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing systemic uptake of the pharmaceutical that is at least about 15% relative to intravenous or subcutaneous administration of an equal amount of the pharmaceutical because the claimed limitations do not appear to constitute any additional method steps and would occur as a natural result of the trans-epithelial administration of the ingestible device of Aran in view of Houzego in view of Trovato).
Regarding claim 791, Aran in view of Houzego in view of Trovato teaches the method of claim 789 wherein the ingestible device is configured to directly deliver the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing an area under the curve (AUC) of the pharmaceutical in systemic circulation over time (AUCTE) that is at least about 10% of the AUC in systemic circulation over time provided by intravenous or subcutaneous administration of an equal amount of the pharmaceutical (the ingestible device of Aran in view of Houzego in view of Trovato is fully capable of directly delivering the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing an area under the curve (AUC) of the pharmaceutical in systemic circulation over time (AUCTE) that is at least about 10% of the AUC in systemic circulation over time provided by intravenous or subcutaneous administration of an equal amount of the pharmaceutical because the claimed limitations do not appear to constitute any additional method steps and would occur as a natural result of the trans-epithelial administration of the ingestible device of Aran in view of Houzego in view of Trovato).
Regarding claim 792, Aran in view of Houzego in view of Trovato teaches the method of claim 789 wherein the ingestible device is configured to directly deliver the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing a maximum plasma concentration (Cmax) of the pharmaceutical in systemic circulation ((Cmax)TE) that is at least about 10% of the Cmax in systemic circulation provided by intravenous or subcutaneous administration of an equal amount of the pharmaceutical (the ingestible device of Aran in view of Houzego in view Trovato is fully capable of directly delivering the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing a maximum plasma concentration (Cmax) of the pharmaceutical in systemic circulation ((Cmax)TE) that is at least about 10% of the Cmax in systemic circulation provided by intravenous or subcutaneous administration of an equal amount of the pharmaceutical because the claimed limitations do not appear to constitute any additional method steps and would occur as a natural result of the trans-epithelial administration of the ingestible device of Aran in view of Houzego in view of Trovato).
Regarding claim 793, Aran in view of Houzego in view of Trovato teaches the method of claim 789, wherein the dispensable substance is released in the small intestine (Aran, intestines, P0009, wherein the intestines include the small intestine).
Regarding claim 794, Aran in view of Houzego in view of Trovato teaches the method of claim 789 wherein the dispensable substance is released in the jejunum (Aran, intestines, P0009, wherein the intestines include the jejunum).
Regarding claim 795, Aran in view of Houzego in view of Trovato teaches the method of claim 789.
The cited references do not teach wherein the compressed gas container provides a fluid pressure of about 225 psig to about 400 psig.
Aran teaches that the devices may be configured to produce various amounts of pressure to propel the active agent formulation out the device with sufficient velocity to penetrate a desired layer of tissue, including power sufficient for transmucosal delivery, P0055. Therefore, pressure exerted is disclosed to be a result effective variable in that changing the amount of pressure affects the velocity of active agent propelled from the device which affects the depth below the tissue surface of delivery of active agent formulation. Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato wherein the compressed gas container provides a fluid pressure of about 225 psig to about 400 psig since it has been held that “where 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).
Regarding claim 796, Aran in view of Houzego in view of Trovato teaches the method of claim 789 wherein the compressed gas drives the dispensable substance through at least one nozzle (Aran, nozzle 104, P0101) to generate the at least one jet.
P0101 and Fig. 1 of Aran teach the nozzle 104 with a nozzle opening, but are silent as to the nozzle opening having a diameter of about 0.3 to 0.5 mm.
An analysis of criticality has been made of Applicant’s specification, and none was apparent on page 6 lines 18-21. The modification of the device 100 of Aran to have a nozzle opening having a diameter of about 0.3 to 0.5 mm will not adversely affect the device of Aran since Aran teaches an ingestible device that may be dimensioned as taught by P0074-0075 of Aran, and thus may be modified with nozzle opening diameters suitable for an ingestible device and trans-epithelial delivery. It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the diameter of the nozzle opening of the device of Aran as claimed for the purpose of trans-epithelial treatment of a condition or disease in a subject, Aran P0093.
Regarding claim 797, Aran in view of Houzego in view of Trovato teaches the method of claim 789 wherein the compressed gas (Aran, CO2, P0101) drives the dispensable substance through the at least one nozzle 104 to generate the at least one jet.
P0101 and Fig. 1 of Aran teach the nozzle 104 with a nozzle opening, but are silent as to the nozzle opening having a diameter of about 0.35 to 0.4 mm.
An analysis of criticality has been made of Applicant’s specification, and none was apparent on page 6 lines 18-21. The modification of the device 100 of Aran to have a nozzle opening having a diameter of about 0.35 to 0.4 mm will not adversely affect the device of Aran since Aran teaches an ingestible device that may be dimensioned as taught by P0074-0075 of Aran, and thus may be modified with nozzle opening diameters suitable for an ingestible device and trans-epithelial delivery. It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the diameter of the nozzle opening of the device of Aran as claimed for the purpose of trans-epithelial treatment of a condition or disease in a subject, Aran P0093.
Regarding claim 798, Aran in view of Houzego in view of Trovato teaches the method of claim 797.
Aran teaches the delivery device is configured to release the contents of the active agent reservoir at high velocity sufficient to deliver the contents through the mucosal layer in the subject and also teaches that velocity can be 10 m/s or more, P0065, but does not explicitly teach an average velocity, wherein the at least one jet of the dispensable substance has an average jet velocity of about 20 m/s to about 50 m/s.
An analysis of criticality has been made, and none was apparent, see page 79 lines 15-25 of the specification. Also, a modification to the device of Aran providing for average jet velocities within the claimed range will not adversely affect the device of Aran since Aran is configured to operate at similar velocities of 10 m/s or more.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato to operate at average jet velocities as claimed for the purpose of trans-epithelial delivery of active agents.
Regarding claim 799, Aran in view of Houzego in view of Trovato teaches the method of claim 789.
Aran P0083 teaches use of active agents with molecular weights between 5 kDa to 100 KDa, but is silent as to the molecular weight of the active agent of the embodiment of P0101 above.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the embodiment of P0101 of Aran with a pharmaceutical within the claimed molecular weight range of about 60 kDa to about 200 kDa since Aran teaches use of active agents within that range for the purpose of diagnosis, treatment, or prevention of a disease or as a component of a medication, Aran P0079.
Regarding claim 800, Aran in view of Houzego in view of Trovato teaches the method of claim 789.
Aran teaches the delivery device is configured to release the contents of the active agent reservoir at high velocity sufficient to deliver the contents through the mucosal layer in the subject and also teaches that velocity can be 10 m/s or more, P0065, but does not explicitly teach an average velocity, wherein the at least one jet of the dispensable substance has an average jet velocity of about 10 m/s to about 50 m/s.
An analysis of criticality has been made, and none was apparent, see page 79 lines 15-25 of the specification. Also, a modification to the device of Aran providing for average jet velocities within the claimed range will not adversely affect the device of Aran since Aran is configured to operate at similar velocities of 10 m/s or more.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato to operate at average jet velocities as claimed for the purpose of trans-epithelial delivery of active agents.
Regarding claim 801, Aran in view of Houzego in view of Trovato teaches the method of claim 789 wherein the dispensable substance comprises insulin (Aran, insulin, P0086 table).
Regarding claim 806, Aran discloses a method of treating a disease or condition, comprising (claims mapped as above for claim 789, unless otherwise noted below): trans-epithelially administering a dispensable substance to the gastrointestinal tract of a patient by orally administering an ingestible device containing the dispensable substance to the patient; the dispensable substance comprising a therapeutically effective amount of a pharmaceutical having a molecular weight of about 3 kDa to about 200 kDa; releasing compressed gas; the released compressed gas contacting and acting on a piston; the piston moving and ejecting the dispensable substance from the ingestible device in the gastrointestinal tract of the patient as at least one jet, providing trans-epithelial delivery of the dispensable substance directly to the submucosa of the gastrointestinal tract of the patient.
Aran teaches the delivery device is configured to release the contents of the active agent reservoir at high velocity sufficient to deliver the contents through the mucosal layer in the subject and also teaches that velocity can be 10 m/s or more, P0065, but does not explicitly teach an average velocity, wherein the at least one jet of the dispensable substance has an average jet velocity of about 20 m/s to about 50 m/s.
An analysis of criticality has been made, and none was apparent, see page 79 lines 15-25 of the specification. Also, a modification to the device of Aran providing for average jet velocities within the claimed range will not adversely affect the device of Aran since Aran is configured to operate at velocities of 10 m/s or more.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran to operate at average jet velocities as claimed for the purpose of trans-epithelial delivery of active agents.
Aran does not teach the compressed gas is pre-pressurized.
However, Houzego teaches an ingestible device wherein pre-pressurized gas (compressed nitrogen or air, P0078) is used as an energy source for expelling a drug, P0075.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of Aran with pre-pressurized gas as taught by Houzego as a simple substitution of one known method of generating pressure to dispense substance from an ingestible capsule for another to obtain predictable results, see MPEP 2143(B). Aran contained a method which differed from the claimed method by the substitution of a pre-pressurized compressed gas for a power reservoir that generated compressed gas from a chemical reaction. Pre-pressurized compressed gas and their function to displace a substance from an ingestible capsule are well known in the art as evidenced by Houzego. One of ordinary skill in the art could have substituted one know element (method for dispensing a substance from an ingestible device by generating compressed gas with a chemical reaction as taught by Aran) for another (method for dispensing a substance from an ingestible device by a pre-pressurized gas as taught by Houzego) and results of the substitution would have been predictable, that is the compressed gas is used for dispensing a substance from the ingestible device.
Houzego teaches use of a pre-pressurized gas, but does not explicitly teach the pre-pressurized gas stored a container.
However, Trovato teaches an ingestible capsule having a pre-pressurized compressed gas container (see P0188 wherein the gas pressurizing module 1602 is a cannister for storing a compressed gas).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to combine the compressed gas of Houzego with the cannister of Trovato for the purpose of storing compressed gas.
Aran in view of Houzego in view of Trovato does not teach the piston providing a fluid pressure of about 100 psig to about 500 psig on the dispensable substance.
Aran teaches that the devices may be configured to produce various amounts of pressure to propel the active agent formulation out the device with sufficient velocity to penetrate a desired layer of tissue, including power sufficient for transmucosal delivery, P0055. Therefore, pressure exerted is disclosed to be a result effective variable in that changing the amount of pressure affects the velocity of active agent propelled from the device which affects the depth below the tissue surface of delivery of active agent formulation. Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato wherein the piston provides a fluid pressure of about 100 psig to about 500 psig on the dispensable substance. since it has been held that “where 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).
Regarding claim 807, Aran in view of Houzego in view of Trovato teaches the method of claim 806 wherein the ingestible device is configured to directly deliver the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing systemic uptake of the pharmaceutical that is at least about 15% relative to intravenous or subcutaneous administration of an equal amount of the pharmaceutical (the ingestible device of Aran is fully capable of directly delivering the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing systemic uptake of the pharmaceutical that is at least about 15% relative to intravenous or subcutaneous administration of an equal amount of the pharmaceutical because the claimed limitations do not appear to constitute any additional method steps and would occur as a natural result of the trans-epithelial administration of the ingestible device of Aran).
Regarding claim 808, Aran in view of Houzego in view of Trovato teaches the method of claim 806 wherein the ingestible device is configured to directly deliver the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing an area under the curve (AUC) of the pharmaceutical in systemic circulation over time (AUCTE) that is at least about 10% of the AUC in systemic circulation over time provided by intravenous or subcutaneous administration of an equal amount of the pharmaceutical (the ingestible device of Aran is fully capable of directly delivering the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing an area under the curve (AUC) of the pharmaceutical in systemic circulation over time (AUCTE) that is at least about 10% of the AUC in systemic circulation over time provided by intravenous or subcutaneous administration of an equal amount of the pharmaceutical because the claimed limitations do not appear to constitute any additional method steps and would occur as a natural result of the trans-epithelial administration of the ingestible device of Aran).
Regarding claim 809, Aran in view of Houzego in view of Trovato teaches the method of claim 806 wherein the ingestible device is configured to directly deliver the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing a maximum plasma concentration (Cmax) of the pharmaceutical in systemic circulation ((Cmax)TE) that is at least about 10% of the Cmax in systemic circulation provided by intravenous or subcutaneous administration of an equal amount of the pharmaceutical (the ingestible device of Aran is fully capable of directly delivering the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing a maximum plasma concentration (Cmax) of the pharmaceutical in systemic circulation ((Cmax)TE) that is at least about 10% of the Cmax in systemic circulation provided by intravenous or subcutaneous administration of an equal amount of the pharmaceutical because the claimed limitations do not appear to constitute any additional method steps and would occur as a natural result of the trans-epithelial administration of the ingestible device of Aran).
Regarding claim 810, Aran in view of Houzego in view of Trovato teaches the method of claim 806 wherein the compressed gas drives the dispensable substance through at least one nozzle (Aran, nozzle 104, P0101) to generate the at least one jet.
P0101 and Fig. 1 of Aran teach the nozzle 104 with a nozzle opening, but are silent as to the nozzle opening having a diameter of about 0.2 to 0.5 mm.
An analysis of criticality has been made of Applicant’s specification, and none was apparent on page 6 lines 18-21. The modification of the device 100 of Aran to have a nozzle opening having a diameter of about 0.2 to 0.5 mm will not adversely affect the device of Aran since Aran teaches an ingestible device that may be dimensioned as taught by P0074-0075 of Aran, and thus may be modified with nozzle opening diameters suitable for an ingestible device and trans-epithelial delivery. It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the diameter of the nozzle opening of the device of Aran as claimed for the purpose of trans-epithelial treatment of a condition or disease in a subject, Aran P0093.
Regarding claim 812, Aran in view of Houzego in view of Trovato teaches the method of claim 806.
The cited references do not teach wherein the compressed gas provides a fluid pressure of about 225 psig to about 400 psig.
However, Aran teaches that the devices may be configured to produce various amounts of pressure to propel the active agent formulation out the device with sufficient velocity to penetrate a desired layer of tissue, including power sufficient for transmucosal delivery, P0055. Therefore, pressure exerted is disclosed to be a result effective variable in that changing the amount of pressure affects the velocity of active agent propelled from the device which affects the depth below the tissue surface of delivery of active agent formulation. Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato wherein the compressed gas provides a fluid pressure of about 225 psig to about 400 psig since it has been held that “where 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).
Regarding claim 814, Aran discloses a method of treating a disease or condition (claims mapped as above for claim 789 unless otherwise noted below), comprising: trans-epithelially delivery of a dispensable substance to the gastrointestinal tract of a patient by orally administering an ingestible device containing the dispensable substance to the patient; the dispensable substance comprising a therapeutically effective amount of a pharmaceutical having a molecular weight of about 3 kDa to about 160 kDa; releasing compressed gas; the released compressed gas contacting and acting on a piston; the piston moving and ejecting the dispensable substance from the ingestible device in the gastrointestinal tract of the patient as at least one jet from at least one nozzle (nozzle 104, P0101), the ingestible device configured to directly deliver the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing systemic uptake of the pharmaceutical that is at least about 15% relative to intravenous or subcutaneous administration of an equal amount of the pharmaceutical (the ingestible device of Aran is fully capable of directly delivering the dispensable substance past the epithelial cell layer of the mucosa and into the submucosa and/or into a region of the mucosa beneath the epithelial layer of the gastrointestinal tract, where it is available for systemic uptake, the trans-epithelial delivery providing systemic uptake of the pharmaceutical that is at least about 15% relative to intravenous or subcutaneous administration of an equal amount of the pharmaceutical because the claimed limitations do not appear to constitute any additional method steps and would occur as a natural result of the trans-epithelial administration of the ingestible device of Aran).
P0101 and Fig. 1 of Aran teach the nozzle 104 with a nozzle opening, but are silent as to the nozzle opening having a diameter of about 0.2 to 0.5 mm.
An analysis of criticality has been made of Applicant’s specification, and none was apparent on page 6 lines 18-21. The modification of the device 100 of Aran to have a nozzle opening having a diameter of about 0.2 to 0.5 mm will not adversely affect the device of Aran since Aran teaches an ingestible device that may be dimensioned as taught by P0074-0075 of Aran, and thus may be modified with nozzle opening diameters suitable for an ingestible device and trans-epithelial delivery. It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the diameter of the nozzle opening of the device of Aran as claimed for the purpose of trans-epithelial treatment of a condition or disease in a subject, Aran P0093.
Aran does not teach the compressed gas is pre-pressurized.
However, Houzego teaches an ingestible device wherein pre-pressurized gas (compressed nitrogen or air, P0078) is used as an energy source for expelling a drug, P0075.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of Aran with pre-pressurized gas as taught by Houzego as a simple substitution of one known method of generating pressure to dispense substance from an ingestible capsule for another to obtain predictable results, see MPEP 2143(B). Aran contained a method which differed from the claimed method by the substitution of a pre-pressurized compressed gas for a power reservoir that generated compressed gas from a chemical reaction. Pre-pressurized compressed gas and their function to displace a substance from an ingestible capsule are well known in the art as evidenced by Houzego. One of ordinary skill in the art could have substituted one know element (method for dispensing a substance from an ingestible device by generating compressed gas with a chemical reaction as taught by Aran) for another (method for dispensing a substance from an ingestible device by a pre-pressurized gas as taught by Houzego) and results of the substitution would have been predictable, that is the compressed gas is used for dispensing a substance from the ingestible device.
Houzego teaches use of a pre-pressurized gas, but does not explicitly teach the pre-pressurized gas stored a container.
However, Trovato teaches an ingestible capsule having a pre-pressurized compressed gas container (see P0188 wherein the gas pressurizing module 1602 is a cannister for storing a compressed gas).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to combine the compressed gas of Houzego with the cannister of Trovato for the purpose of storing compressed gas.
Aran in view of Houzego in view of Trovato does not teach the piston providing a fluid pressure of about 100 psig to about 500 psig on the dispensable substance.
Aran teaches that the devices may be configured to produce various amounts of pressure to propel the active agent formulation out the device with sufficient velocity to penetrate a desired layer of tissue, including power sufficient for transmucosal delivery, P0055. Therefore, pressure exerted is disclosed to be a result effective variable in that changing the amount of pressure affects the velocity of active agent propelled from the device which affects the depth below the tissue surface of delivery of active agent formulation. Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato wherein the piston provides a fluid pressure of about 100 psig to about 500 psig on the dispensable substance. since it has been held that “where 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).
Regarding claim 816, Aran in view of Houzego in view of Trovato teaches the method of claim 814.
The cited references do not teach wherein the compressed gas provides a fluid pressure of about 225 psig to about 400 psig.
However, Aran teaches that the devices may be configured to produce various amounts of pressure to propel the active agent formulation out the device with sufficient velocity to penetrate a desired layer of tissue, including power sufficient for transmucosal delivery, P0055. Therefore, pressure exerted is disclosed to be a result effective variable in that changing the amount of pressure affects the velocity of active agent propelled from the device which affects the depth below the tissue surface of delivery of active agent formulation. Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato wherein the compressed gas provides a fluid pressure of about 225 psig to about 400 psig since it has been held that “where 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).
Regarding claim 817, Aran in view of Houzego in view of Trovato teaches the method of claim 814.
Aran teaches the delivery device is configured to release the contents of the active agent reservoir at high velocity sufficient to deliver the contents through the mucosal layer in the subject and also teaches that velocity can be 10 m/s or more, P0065, but does not explicitly teach an average velocity, wherein the at least one jet of the dispensable substance has an average jet velocity of about 20 m/s to about 50 m/s.
An analysis of criticality has been made, and none was apparent, see page 79 lines 15-25 of the specification. Also, a modification to the device of Aran providing for average jet velocities within the claimed range will not adversely affect the device of Aran since Aran is configured to operate at velocities of 10 m/s or more.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato to operate at average jet velocities as claimed for the purpose of trans-epithelial delivery of active agents.
Regarding claim 818, Aran in view of Houzego in view of Trovato teaches the method of claim 814.
Aran teaches the delivery device is configured to release the contents of the active agent reservoir at high velocity sufficient to deliver the contents through the mucosal layer in the subject and also teaches that velocity can be 10 m/s or more, P0065, but does not explicitly teach an average velocity, wherein the at least one jet of the dispensable substance has an average jet velocity of about 30 m/s to about 50 m/s.
An analysis of criticality has been made, and none was apparent, see page 79 lines 15-25 of the specification. Also, a modification to the device of Aran providing for average jet velocities within the claimed range will not adversely affect the device of Aran since Aran is configured to operate at similar velocities of 10 m/s or more.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato to operate at average jet velocities as claimed for the purpose of trans-epithelial delivery of active agents.
Regarding claim 819, Aran in view of Houzego in view of Trovato teaches the method of claim 789 wherein the dispensable substance is a liquid (Aran, liquid, P0029).
Claims 802 and 805 are rejected under 35 U.S.C. 103 as being unpatentable over Aran in view of Houzego in view of Trovato in view of Imran US 2013/0172257 A1.
Regarding claim 802, Aran in view of Houzego in view of Trovato teaches the method of claim 789.
Aran in view of Houzego in view of Trovato do not teach wherein the dispensable substance comprises adalimumab.
However, Imran teaches a therapeutic agent for delivery using a swallowable drug delivery device wherein the dispensable substance comprises adalimumab, table 1 page 19.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato to deliver adalimumab as taught by Imran for the purpose of treating hepatis, Imran table 1.
Regarding claim 805, Aran in view of Houzego in view of Trovato teaches the method of claim 789.
Aran in view of Houzego in view of Trovato does not teach wherein the dispensable substance comprises liraglutide.
However, Imran teaches a therapeutic agent for delivery using a swallowable drug delivery device wherein the dispensable substance comprises liraglutide, table 1 page 19.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato to deliver liraglutide as taught by Imran for the purpose of treating diabetes, Imran P0004.
Claims 803 and 804 are rejected under 35 U.S.C. 103 as being unpatentable over Aran in view of Houzego in view of Trovato in view of Berenbaum et al. (Berenbaum) US 2015/0209411 A1.
Regarding claim 803, Aran in view of Houzego in view of Trovato teaches the method of claim 789.
Aran in view of Houzego in view of Trovato does not teach wherein the dispensable substance comprises dulaglutide.
However, Berenbaum teaches ingestible compositions administered orally, P0024, including dulaglutide P0016.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato with dulaglutide as taught by Berenbaum for the purpose of treating osteoarthritis, P0011 of Berenbaum.
Regarding claim 804, Aran in view of Houzego in view of Trovato teaches the method of claim 789 wherein the dispensable substance comprises semaglutide.
Aran in view of Houzego in view of Trovato does not teach wherein the dispensable substance comprises semaglutide.
However, Berenbaum teaches ingestible compositions administered orally, P0024, including semaglutide P0016.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the device of Aran in view of Houzego in view of Trovato with semaglutide as taught by Berenbaum for the purpose of treating osteoarthritis, P0011 of Berenbaum.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN A DOUBRAVA whose telephone number is (408)918-7561. The examiner can normally be reached M-F 9-5 Pacific Time.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov