DETAILED ACTION
Claims 1, 5-19, 36, 40-41, 63-74, and 97 are pending.
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 .
Priority
The instant application filed 11/2/2023 is a National Stage entry of PCT/US2022/072114, with an International Filing Date of 5/4/2022. PCT/US2022/072114 Claims Priority from Provisional Application 63184734, filed 5/5/2021.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 5-19, 36, and 40-41 in the Reply filed on 6/12/2026, is acknowledged.
Claims 63-74 and 97 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the Reply.
Claims 1, 5-19, 36, and 40-41 are present for Examination and the subject of the Office Action below.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 6/10/2024 and 6/12/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statements are being considered by the Examiner.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 5-19, 36, and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Kanasty et al. US 2020/0146979 A1; Jones et al., “Population Pharmacokinetics of a Monthly Buprenorphine Depot Injection for the Treatment of Opioid Use Disorder: A Combined Analysis of Phase II and Phase III Trials Clinical Pharmacokinetics,” (2021) 60:527–540; and Coe et al. “Buprenorphine Pharmacology Review: Update on Transmucosal and Long-Acting Formulations,” J Addict Med. 2019; 13(2): 93–103.
Claim 1 is directed towards a gastric residence system comprising: at least one co-extruded drug-eluting component comprising a carrier polymer, buprenorphine or a salt thereof, and naloxone or a salt thereof; and a rate-modulating release film coating the at least one co-extruded drug-eluting component, wherein the gastric residence system is configured to be maintained within a stomach of a human body for at least 48 hours and to release buprenorphine for at least 48 hours, and the at least one co-extruded drug eluting component with the rate-modulating release film is configured to release at least 10 % of the buprenorphine or the salt thereof after the first 24 hours of residence within the stomach and at least 10 % of the naloxone or the salt thereof after the first 24 hours of residence within the stomach.
Kanasty teaches gastric residence systems, see Abstract.
Kanasty teaches [0154], release rate-modulating polymer films can also be integrated onto segments by co-extrusion, where the segment formulation is co-extruded with a surrounding thin layer of the release rate-modulating polymer film.
Kanasty teaches [0267], the choice of the individual polymers for the carrier polymer, coupling polymer, and elastomer influence many properties of the system, such as drug elution rate (dependent on the carrier polymer, as well as other factors), the residence time of the system (dependent on the degradation of any of the polymers, principally the coupling polymers), the uncoupling time of the system if it passes into the intestine (dependent primarily on the enteric degradation rate of the coupling polymer, as discussed herein), and the shelf life of the system in its compressed form (dependent primarily on properties of the elastomer).
Kanasty teaches [0002], the invention relates to systems which remain in the stomach for extended periods for sustained release of pharmaceuticals, and methods of use thereof.
Kanasty teaches [0187] agents which can be administered to or via the gastrointestinal tract can be used in the gastric residence systems of the invention. The agent is blended with the carrier polymer, and any other excipients or other additives to the carrier polymer, and formed into a segment for use in a gastric residence system. Agents include, but are not limited to, drugs…. analgesics, such as buprenorphine; opioid antagonists, such as naloxone…
Kanasty teaches that the release profile can be adjusted to the drugs desired exposure for efficacy, and that when looking at the Figures, one sees that several embodiments were able to achieve sustained drug release over 4-10 days and can be adjusted to release ~10% per day for 10 days. An example is seen in Figure 23. With 10% released on day 1, followed by 10% more each day up to 10 days.
Kanasty doesn’t teach the exact embodiment of buprenorphine and naloxone.
Jones teaches the desirable plasma levels when considering a long-acting formulation of buprenorphine. The teaching states, “Withdrawal symptoms were controlled when at least 50% of mu-opioid receptors were occupied (corresponding to plasma levels ≥ 1 ng/mL), while subjective effects of an exogenous opioid agonist were controlled when more than 70–80% of mu-opioid receptors were occupied (corresponding to plasma levels ≥ 2–3 ng/mL. These results were pivotal in defining target buprenorphine plasma concentrations of at least 2–3 ng/mL, which drove the clinical development of BUP-XR.”
Coe teaches why naloxone is used in combination, mainly to deter abuse. The typical ratio is 4:1, buprenorphine:naloxone. Coe states, “When buprenorphine/naloxone is ingested via prescribed routes, naloxone is essentially inert due to poor oral and sublingual bioavailability followed by first-pass metabolism and elimination; however, when insufflated or injected, naloxone is bioavailable and can precipitate withdrawal.” As such the compound is simply used to stop abuse and would be added to prevent crushing and snorting the dose.
A person of ordinary skill in the art would look to make a gastric residence system with buprenorphine and naloxone as a gastric residence system is longer acting than the available oral routes (daily administration) and doesn’t require an injection or surgical insertion. This would therefore improve patient compliance as the patient wouldn’t be required to keep up with once-a-day oral dosing. Moreover, the gastric residence system doesn’t require an injection or surgical insertion meaning the dosing is easier and less painful and having no risk of infection. This provides motivation to use the gastric residence system with buprenorphine:naloxone. One would look to have a longer time of exposure than the known oral formulation. One would target around ~1-3 ng/ml steady state plasma concentration, and one would look to be in the system for at least 2 days to 28 days to be an improvement in oral dosing. However, from Kanasty one could easily envisage 10-14 day exposure from one gastric residence system based on most of the examples.
The dependent claims are all directed to simple design choices and routine optimization to achieve ~1-3 ng/ml steady state plasma concentration of buprenorphine while deterring abuse by including naloxone. “Design choice” simply means that the selected polymers, formulants, or route of manufacture do not have significance to patentability as one could use the polymers interchangeably, the formulants interchangeably, and the concentrations and methods of manufacturing could be varied without changing the principle of operation, also the secondary structure doesn’t affect the principle either, as any secondary structure taught in the art by Kanasty would be able to perform the desired outcome with interchangeability.
“Mere design choice” is obvious, a difference from the prior art that is only a design choice (no unexpected result, no different function, no solution to a stated problem) is obvious and therefore unpatentable. Key cases:
In re Kuhle, 526 F.2d 553 (C.C.P.A. 1975)The particular placement of an electrical contact “solves no stated problem and presents no unexpected result and would be an obvious matter of design choice within the skill of the art.”
In re Chu, 66 F.3d 292 (Fed. Cir. 1995)“Design choice” is an appropriate rationale when the applicant “fails to set forth any reasons why the differences between the claimed invention and the prior art would result in a different function.”
In re Gal, 980 F.2d 717 (Fed. Cir. 1992)A finding of obvious design choice is precluded when the claimed structure performs a different function from the prior art.
The important principle is, selection among known alternatives is obvious unless the applicant shows unexpected results or a new function. That is not the case of the claims discussed, as there appears to be nothing unexpected or a new function.
The dependent claims directed to the secondary structure are design choices, for example instant claim 5 calls for one co-extruded potion to have naloxone and a 2nd co-extruded portion to have buprenorphine and naloxone. Applicant could explain the relevance, but this is simply a design choice without significance as Applicant has not shown any importance to this configuration. Instant claims 6 required embedded, and instant claim 7 required layered. These are all potential design features as taught by Kanasty in the “Manufacture/Assembly of System: Co-Extrusion” section stating at [0228].
Instant claim 9 requires a ratio of 4:1 of one co-extruded portion to the 2nd portion. There is no explanation or significance shown to this ratio.
Instant claims 10-11 are directed to drug loading levels. The instant claims require 35-50 wt % of buprenorphine in the first co-extruded portion and 2-7% of the naloxone in the first co-extruded portion. This falls within the teaching of Kanasty to the drug loading range. Kanasty teaches drug loading at [0193], and over the next few paragraphs notes the loading can be low or high. The range seems roughly from about 10% to about 60%, for the segments. The segments can be made by co-extrusion.
Instant claim 12 requires the first co-extruded portion comprises 35-50 wt% polycaprolactone. Kanasty states [0184] polycaprolactone (PCL) is a preferred carrier polymer. Kanasty [0281] gives a typical case. A variety of carrier polymer-agent segment formulations can be used with any given release rate-modulating film to provide desired release characteristics from the film-coated segment. Likewise, a variety of release rate-modulating films can be used with any given carrier polymer-agent segment formulation. One useful combination of carrier polymer-agent/film comprises a segment with about 15% to about 40% agent, about 3% to about 15% of excipients selected from one or more of P407, silica, and vitamin E succinate, with the balance of the segment made up of polycaprolactone (PCL); and a release rate-modulating film that is about 75% to about 95% polycaprolactone with the balance of the film comprising copovidone porogen, where the weight of the film is about 0.5% to about 2% of the weight of the underlying segment, and/or where the thickness of the film ranges from about 3 microns to about 10 microns. This example would result in the 15-40 agent, 3-15 excipients, and therefore 45-82% is polycaprolactone as the balance before the film coating.
Moreover, to address instant claim 12, Kanasty shows examples with a variety of different formulations of the segments, many of which include PCL in the ranges overlapping the instantly claimed range. Again, this appears to be a design choice, and not a patentable feature.
Instant claim 13 requires comprises polyethylene glycol and a poloxamer. These polymers are used throughout Kanasty, and appear to be design choice. This follows for instant claims 14-16, as they simply are part of the design and the specifics outlined do not change the fundamental nature of the product. Which is to simply deliver buprenorphine over a time period of 2-28 days while maintaining ~3 ng/ml plasma concentration. The polymers and the concentrations are not significant to the result.
Claim 17 again is to a nebulous single portion of the whole system, requiring that the at least one co-extruded drug-eluting component comprises 30 mg to 40 mg of buprenorphine or a salt thereof. This again is in the known range of the drug in the single portion, but the amount will simply be adjusted to achieve the duration of treatment over time to maintain ~3 ng/ml plasma concentration. Therefore, the amount is corelated to the need of the patient and known in the art, as such when using this known technology, one would arrive at this number with routine optimization.
Instant claim 18 is similar with regards to the amount of naloxone. The amount needed in the formulation is well known. As one would use enough naloxone as to stop abuse if the “system” was destroyed and turned into something one could snort. The goal being to stop the abuse of buprenorphine. The ratio is roughly 4:1 as known in the art. As such one would arrive at the proper amount when designing the “gastric residence system” with routine optimization and proper design.
Instant claim 19 is directed to the design of the secondary structure of the “system” the claim states, the gastric residence system comprises a central elastomer and a plurality of arms, each arm of the plurality of arms comprising a proximal end affixed to the central elastomer and a distal end, wherein each arm of the plurality of arms extends radially from the central elastomer, and at least one arm of the plurality of arms comprises the at least one co-extruded drug-eluting component.
Instantly claimed Figure 1A:
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Kanasty Figure 1A:
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The secondary structure is clearly taught by Kanasty.
Instant claims 36, 40, and 41 are directed to a broader genus of a “gastric residence system” as these claims are similar to instant claim 1 but they do not require co-extrusion. Given this claim would include the co-extrusion design, these claims are also found to be obvious.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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