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 .
Status of the Claims
Claims 3-9, 11-30, 32, 36, 39, 42-45, 49, 50, 53, 54, 56, 58-81, 83-89, and 91-100 have been cancelled previously.
Claims 1, 2, 10, 31, 33-35, 37, 38, 40, 41, 46-48, 51, 52, 55, 57, 82, and 90 are pending and under current examination.
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.
Claims 2 and 41 are 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 2, lines 21-23, recites “an optional fifth inert segment attached to the drug eluting segment; a third disintegrating matrix segment attached to the optional fifth inert segment”. The claim is indefinite because the fifth inert segment is optional; however, the third disintegrating matrix segment is not unambiguously optional therefore it’s not clear whether it must be present when the fifth inert segment is absent. As such the scope of the claimed invention is uncertain.
Claim 41 recites a period, in lines 10 and 13, in the middle of the claim. As such the language following the periods does not definitively limit the invention. See MPEP 608.01(m).
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 10 is rejected under 35 U.S.C. 103 as being unpatentable over Bellinger et al. (US 2019/0262265; publication date: 08/29/2019; cited in the IDS filed 09/15/2023) in view of Kanasty et al. (Journal of Controlled Release vol 303 pages 34-41; publication year: 2019) and further in view of Van Nest (US 20010046967 Publication date 11/29/2001) and Bellinger (US 2019/0254966; publication date: 08/22/2019; cited in the IDS filed 09/15/2023).
Independent claim 10 claims a gastric residence system comprising: six arms affixed to a central elastomer, wherein at least one arm comprises a drug-eluting segment; each arm comprising a proximal end, a distal end, and an outer surface therebetween; wherein the proximal end of each arm is attached to the elastomer component and projects radially from the elastomer component, each arm having its distal end not attached to the elastomer component and located at a larger radial distance from the elastomer component than the proximal end; wherein the at least one arm comprising a drug eluting segment comprises: a first inert segment; a first disintegrating matrix segment attached to the first inert segment; a second inert segment attached to the first disintegrating matrix segment; a second disintegrating matrix segment attached to the second inert segment; a third inert segment attached to the second disintegrating matrix segment; a fourth inert segment attached to the third inert segment; the drug eluting segment attached to the fourth inert segment, wherein the drug eluting segment comprises a carrier polymer, and risperidone or a salt thereof, and wherein the drug eluting segment further comprises a coating comprising a release rate-modulating polymer film; a fifth inert segment attached to the drug eluting segment; and an optional filament circumferentially connecting each arm.
Bellinger discloses a gastric residence system with optimal residence properties when the systems are deployed in the stomach (abstract): In para 0169 Bellinger describes Figure 2, which depicts a system having at least 3 arms (in this case, 6 arms) affixed to a central elastomer:
[A] stellate system 200 is shown schematically in FIG. 2. Multiple “arms” (only one such arm, 208, is labeled for clarity) are affixed to asterisk-shaped (disk-shaped) central elastomer 206. The arms depicted in FIG. 2 are comprised of segments 202 and 203, joined by a coupling polymer 204. This configuration permits the system to be folded or compacted in the manner shown for the system 290 in FIG. 2C. Only two arms are shown in FIG. 2C for clarity, and only one arm (298) is labeled for clarity. The central elastomer 296 is folded, such that the overall length of the system is reduced by approximately a factor of two, and the system can be conveniently placed in a container such as a capsule or other container suitable for oral administration.
Figure 2 is reproduced here:
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An arm has carrier polymer agent components that are also referred to as “elongate member” and the “elongate member comprising a proximal end, a distal end, and an outer surface therebetween; wherein the proximal end of each elongate member can be attached to the elastomer component and projects radially from the elastomer component, each elongate member having its distal end not attached to the elastomer component and located at a larger radial distance from the elastomer component than the proximal end”. Therapeutic agent is eluted from the carrier polymer-agent components (i.e. a drug-eluting segment comprising a carrier polymer and a drug; 0164). The polymer-agent component (drug eluting segment) may be configured to deliver risperidone as the drug (0270).
Bellinger does not disclose a coating over the drug eluting segment comprising a release rate-modulating polymer film.
Kanasty discloses a stellate gastroretentive dosage form (figure 1, page 35) wherein coating the drug releasing polymer matrix leads to near linear drug release for a memantine formulation (abstract, title, figure 1, and figure 3). The coating is formed from a polymer (section 4.1, page 40), which as can be seen from figure 3 modulates the release rate of the drug from the polymer matrix.
It would have been prima facie obvious to coat the drug eluting segment with a release rate modulating polymer film. The skilled artisan would have been motivated to do so in order to provide steady consistent release of drug, and in turn consistent plasma profiles, after administration. The skilled artisan would have had a reasonable expectation of success because this had been achieved with a different drug, as demonstrated by Kanasty.
The relevant disclosures of Bellinger ‘265, and Kanasty are set forth above and render obvious a gastric residence system comprising: at least three arms affixed to a central elastomer, wherein at least one arm comprises a drug-eluting segment, each arm comprising a proximal end, a distal end, and an outer surface therebetween; wherein the proximal end of each arm is attached to the elastomer component and projects radially from the elastomer component, each arm having its distal end not attached to the elastomer component and located at a larger radial distance from the elastomer component than the proximal end; wherein the drug eluting segment comprises a carrier polymer, and risperidone or a salt thereof; wherein the drug eluting segment further comprises a coating comprising a release rate- modulating polymer film.
Claim 10 also requires:
the at least one arm comprising a drug eluting segment to comprise:
a first disintegrating matrix segment;
a first inert segment attached to the first disintegrating matrix segment;
a second disintegrating matrix segment attached to the first inert segment; a second inert segment attached to the second disintegrating matrix segment;
a third inert segment attached to the second disintegrating matrix segment; a fourth inert segment attached to the third inert segment; the drug eluting segment attached to the fourth inert segment; a fifth inert segment attached to the drug eluting segment, and in the case of instant claim 10, the filament is optional.
Bellinger discloses further that the arms can be comprised of “at least two segments” (0063), thus Bellinger discloses arms comprising multiple segments. The segments are adhered together by “coupling polymers”, which are polymers suitable for coupling other polymers together (0145). The arms can contain an anchor segment, a linker segment, a interfacing polymer segment, and a carrier polymer-drug segment (0007 and 0008). The various segments are formed from polymers that control their dissolution in different portions of the gastrointestinal tract; in para 0165, Bellinger discloses further:
The gastric residence system passes out of the stomach at an appropriate time point, that is, once the useful therapeutic agent delivery lifetime of the system has been reached, or at a reasonable fraction of the useful therapeutic agent delivery lifetime of the system. This is accomplished by suitable choice of the coupling polymer components and the dimensions of the system. In its intact, uncompressed form, the gastric residence system is designed to resist passage through the pyloric sphincter. That is, in its intact form, the gastric residence system is too large to pass through the pyloric sphincter. The coupling polymer components are chosen such that they gradually weaken and/or degrade over the residence period in the stomach. When the coupling polymer components are sufficiently weakened or degraded, the gastric residence system breaks apart into smaller pieces, which are able to pass through the pyloric sphincter. The system then passes through the intestines and is eliminated from the patient. (Emphasis added.)
In para 0167, Bellinger discloses:
In its desired mode of operation, the gastric residence systems have their intact uncompressed form while resident in the stomach, and do not pass through the pylorus until they break apart after the desired residence time. If a gastric residence system passes intact into the intestine, it has the potential to result in intestinal blockage. Thus, the gastric residence systems are designed to uncouple rapidly in the intestinal environment by dissolution of the coupling polymer, within 48 hours, preferably within 24 hours, more preferably within 12 hours, yet more preferably within 1-2 hours, so as to avoid potential intestinal blockage. This is readily accomplished by using enteric polymers as the coupling polymers. Enteric polymers are relatively resistant to the acidic pH levels encountered in the stomach, but dissolve rapidly at the higher pH levels found in the duodenum. Use of enteric coupling polymers as safety elements protects against undesired passage of the intact gastric residence system into the small intestine. The use of enteric coupling polymers also provides a manner of removing the gastric residence system prior to its designed residence time; should the system need to be removed, the patient can drink a mildly alkaline solution, such as a sodium bicarbonate solution, or take an antacid preparation such as hydrated magnesium hydroxide (milk of magnesia) or calcium carbonate, which will raise the pH level in the stomach and cause rapid degradation of the enteric coupling polymers. The gastric residence system will then break apart and be eliminated from the patient. (Emphasis added.)
The linkers can be enteric linkers such as HPMCAS combined with PCL (0008 and 0009; emphasis added) or time dependent linkers (0007). The examiner considers the blend of HPMCAS and PCL to fall within the scope of “disintegrating matrix” recited in the instant claims, particularly in view of the instant specification, which states e.g. “some embodiments, the enteric disintegrating matrix comprises about 59 wt% to about 69 wt% HPMCAS, about 29 wt% to about 39 wt% PCL” (instant specification: 0109). The carrier polymer-agent (i.e. drug eluting segment) is preferably comprised of PCL and a drug (0217). The intercomponent anchors may be polycarbonate, polyphenylsulfone, a polyphenylene ether-polystyrene blend, polyphenylene ether, polystyrene, and polyether ether ketone (0012). These polymers also fall within the scope of the term “inert matrix”, as they are non-biodegradable (see Van Nest: 0087) Typically, when attaching two different elements, where each element comprises a common polymer, the common polymer is used as the interfacing polymer. For example, if a linker comprising 50% HPMCAS and 50% PCL is to be attached to a carrier polymer-therapeutic agent component comprising PCL and a drug, then PCL can be used as the interfacing polymer (0305).
Thus, Bellinger discloses a stellate gastroretentive drug delivery system comprising multi-segment arms formed from enteric matrices (disintegrating) or non-enteric matrices (inert) and teaches that the rate at which the enteric matrix segments degrade can be used to control the duration of time the system remains in the stomach before passing through the pyloric sphincter into the intestines allowing for drug elution from the carrier polymer-drug segments for a predetermined amount of time.
Bellinger ‘265 does not disclose an example gastroretentive system having the arrangement delineated in instant claim 10.
Bellinger ‘966, describing a very similar gastrorententive dosage form (see: title, abstract, figures), teaches that use of multiple linker sections permits the gastric residence system to break into relatively small pieces after desired residence time for easier passage through the gastrointestinal tract (0090). Bellinger ‘966 teaches further advantages of multi-segment stellate gastroretentive systems including protection against undesired passage of the system into the small intestine, and easy removal if such is required prior to the designed residence time by consumption of an alkaline solution (0087). Bellinger also teaches that curved ends allow the system to fit more snugly into the capsule prior to administration (0097). Finally, Bellinger ‘966 teaches that the ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the system (abstract).
In view of the teachings set forth above, one having ordinary skill in the art would have understood that stellate gastroretentive systems can be designed to deliver risperidone with arms sufficiently long that the system does not pass out of the stomach, wherein the arms are comprised of multiple segments, some of which are degradable such that the arms break apart over time into pieces small enough to pass out of the stomach, where they are subsequently excreted, and that an additional curved cap segment would allow for longer arms, while permitting the folded system to fit snugly within a smaller capsule for easy swallowing.
Claim 10 is considered prima facie obvious, although the specific arrangement is not taught in a single embodiment or example, because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. Absent evidence of unexpectedly superior performance for the claimed arrangement of prior art segments within the arm, the examiner considers this to have been combining prior art elements according to known methods to yield predictable results (see MPEP 2143(I)(A)).
Claims 57, 82, and 90 are rejected under 35 U.S.C. 103 as being unpatentable over Bellinger et al. (US 2019/0262265; publication date: 08/29/2019; cited in the IDS filed 09/15/2023) in view of Kanasty et al. (Journal of Controlled Release vol 303 pages 34-41; publication year: 2019) and further in view of Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019).
With regard to independent claims 1, 2, 10, 31, and 57, Bellinger discloses a gastric residence system with optimal residence properties when the systems are deployed in the stomach (abstract): In para 0169 Bellinger describes Figure 2, which depicts a system having at least 3 arms (in this case, 6 arms) affixed to a central elastomer:
[A] stellate system 200 is shown schematically in FIG. 2. Multiple “arms” (only one such arm, 208, is labeled for clarity) are affixed to asterisk-shaped (disk-shaped) central elastomer 206. The arms depicted in FIG. 2 are comprised of segments 202 and 203, joined by a coupling polymer 204. This configuration permits the system to be folded or compacted in the manner shown for the system 290 in FIG. 2C. Only two arms are shown in FIG. 2C for clarity, and only one arm (298) is labeled for clarity. The central elastomer 296 is folded, such that the overall length of the system is reduced by approximately a factor of two, and the system can be conveniently placed in a container such as a capsule or other container suitable for oral administration.
Figure 2 is reproduced here:
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An arm has carrier polymer agent components that are also referred to as “elongate member” and the “elongate member comprising a proximal end, a distal end, and an outer surface therebetween; wherein the proximal end of each elongate member can be attached to the elastomer component and projects radially from the elastomer component, each elongate member having its distal end not attached to the elastomer component and located at a larger radial distance from the elastomer component than the proximal end”. Therapeutic agent is eluted from the carrier polymer-agent components (i.e. a drug-eluting segment comprising a carrier polymer and a drug; 0164). The polymer-agent component (drug eluting segment) may be configured to deliver risperidone as the drug (0270).
Bellinger does not disclose a coating over the drug eluting segment comprising a release rate-modulating polymer film.
Kanasty discloses a stellate gastroretentive dosage form (figure 1, page 35) wherein coating the drug releasing polymer matrix leads to near linear drug release for a memantine formulation (abstract, title, figure 1, and figure 3). The coating is formed from a polymer (section 4.1, page 40), which as can be seen from figure 3 modulates the release rate of the drug from the polymer matrix.
It would have been prima facie obvious to coat the drug eluting segment with a release rate modulating polymer film. The skilled artisan would have been motivated to do so in order to provide steady consistent release of drug, and in turn consistent plasma profiles, after administration. The skilled artisan would have had a reasonable expectation of success because this had been achieved with a different drug, as demonstrated by Kanasty.
Bellinger also does not disclose a filament circumferentially connecting each arm; however, Bellinger discloses that there may be webbing between the arms of the dosage form (figure 35). The webbing can present to varying extents (figure 35A-D) and provides “resistance to x-y bending than the unwebbed designs; as the amount of webbing is increased, the x-y bending force increases” (0191). Bellinger discloses further a relationship between “[r]esistance to x-y bending and “amount of webbing between elastomer arms” and also with the durometer of the central elastomer asterisk member (0192). Designing the system to have optimal x-y bending force such that it can be folded into a capsule but remails extended once it has expanded in the stomach is essential for delivery and retention in the stomach for the intended duration (0190). One having ordinary skill in the art would have recognized that the web in Bellinger’s invention connects the arms, contributing to holding them in place once the device has expanded in the stomach.
Fitzpatrick, in the analogous art of gastroretentive dosage forms (page 1), discloses some physical linkages that may connect elements of a gastroretentive device, such as fibrous materials including suture material or threads (page 8).
It would have been prima facie obvious to connect the arms of the stellate gastroretentive dosage form disclosed by Bellinger using a thread or string (which the examiner considers to fall within the scope of the term “filament” recited in the instant claims) in place of the of the webbing because one of ordinary skill would have recognized it to serve the same purpose of holding the structure in the desired conformation. See MPEP 2143(I)(B).
Claims 82 and 90 require various pharmacodynamic properties of the formulation for risperidone delivery, in the alternative. The examiner considers optimizing risperidone release to have been a matter of routine testing for one of ordinary skill in view of the teachings provided by Bellinger on how to achieve steady state extended release of any drug, including risperidone, and for this reason the examiner does not consider the functional language of claims 82 and 90 to patentably define over the cited prior art.
Claims 1, 2, 10, 31, 33, 35, 37, 40, 41, 46-48, 51, 52, and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Bellinger et al. (US 2019/0262265; publication date: 08/29/2019; cited in the IDS filed 09/15/2023), Kanasty et al. (Journal of Controlled Release vol 303 pages 34-41; publication year: 2019), and Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019) as applied to claims 57, 82, and 90 above, and further in view of Van Nest (US 20010046967 Publication date 11/29/2001) and Bellinger (US 2019/0254966; publication date: 08/22/2019; cited in the IDS filed 09/15/2023).
The relevant disclosures of Bellinger ‘265, Kanasty, and Fitzpatrick are set forth above and render obvious a gastric residence system comprising: at least three arms affixed to a central elastomer, wherein at least one arm comprises a drug-eluting segment, each arm comprising a proximal end, a distal end, and an outer surface therebetween; wherein the proximal end of each arm is attached to the elastomer component and projects radially from the elastomer component, each arm having its distal end not attached to the elastomer component and located at a larger radial distance from the elastomer component than the proximal end; wherein the drug eluting segment comprises a carrier polymer, and risperidone or a salt thereof; wherein the drug eluting segment further comprises a coating comprising a release rate- modulating polymer film; and a filament circumferentially connecting each arm.
Claims 1, 2, 10, and 31 recite all of the limitations as addressed above and further limit the structure of the arms:
Claims 1, 2, 10, and 31 each require:
the at least one arm comprising a drug eluting segment to comprise:
a first disintegrating matrix segment;
a first inert segment attached to the first disintegrating matrix segment;
a second disintegrating matrix segment attached to the first inert segment; a second inert segment attached to the second disintegrating matrix segment;
Claim 1 adds the further limitation that the at least one arm comprising a drug eluting segment also comprises a third inert segment attached to the second disintegrating matrix segment; a fourth inert segment attached to the third inert segment; the drug eluting segment attached to the fourth inert segment, an optional fifth inert segment attached to the drug eluting segment; and a third disintegrating matrix segment which is attached to the optional fifth inert segment when the optional fifth inert segment is present, or which is attached to the drug eluting segment when the optional fifth inert segment is not present.
Claim 2 adds the further limitation that the at least one arm comprising a drug eluting segment also comprises a third inert segment attached to the second disintegrating matrix segment; a fourth inert segment attached to the third inert segment; the drug eluting segment attached to the fourth inert segment; an optional fifth inert segment attached to the drug eluting segment; a third disintegrating matrix segment attached to the optional fifth inert segment.
Claim 10 adds the further limitation that a third inert segment attached to the second disintegrating matrix segment; a fourth inert segment attached to the third inert segment; the drug eluting segment attached to the fourth inert segment; a fifth inert segment attached to the drug eluting segment, and in the case of instant claim 10, the filament is optional.
Claim 31 further requires the drug eluting segment to be attached to the second inert segment and a third inert segment attached to the drug eluting segment.
Bellinger discloses further that the arms can be comprised of “at least two segments” (0063), thus Bellinger discloses arms comprising multiple segments. The segments are adhered together by “coupling polymers”, which are polymers suitable for coupling other polymers together (0145). The arms can contain an anchor segment, a linker segment, a interfacing polymer segment, and a carrier polymer-drug segment (0007 and 0008). The various segments are formed from polymers that control their dissolution in different portions of the gastrointestinal tract; in para 0165, Bellinger discloses further:
The gastric residence system passes out of the stomach at an appropriate time point, that is, once the useful therapeutic agent delivery lifetime of the system has been reached, or at a reasonable fraction of the useful therapeutic agent delivery lifetime of the system. This is accomplished by suitable choice of the coupling polymer components and the dimensions of the system. In its intact, uncompressed form, the gastric residence system is designed to resist passage through the pyloric sphincter. That is, in its intact form, the gastric residence system is too large to pass through the pyloric sphincter. The coupling polymer components are chosen such that they gradually weaken and/or degrade over the residence period in the stomach. When the coupling polymer components are sufficiently weakened or degraded, the gastric residence system breaks apart into smaller pieces, which are able to pass through the pyloric sphincter. The system then passes through the intestines and is eliminated from the patient. (Emphasis added.)
In para 0167, Bellinger discloses:
In its desired mode of operation, the gastric residence systems have their intact uncompressed form while resident in the stomach, and do not pass through the pylorus until they break apart after the desired residence time. If a gastric residence system passes intact into the intestine, it has the potential to result in intestinal blockage. Thus, the gastric residence systems are designed to uncouple rapidly in the intestinal environment by dissolution of the coupling polymer, within 48 hours, preferably within 24 hours, more preferably within 12 hours, yet more preferably within 1-2 hours, so as to avoid potential intestinal blockage. This is readily accomplished by using enteric polymers as the coupling polymers. Enteric polymers are relatively resistant to the acidic pH levels encountered in the stomach, but dissolve rapidly at the higher pH levels found in the duodenum. Use of enteric coupling polymers as safety elements protects against undesired passage of the intact gastric residence system into the small intestine. The use of enteric coupling polymers also provides a manner of removing the gastric residence system prior to its designed residence time; should the system need to be removed, the patient can drink a mildly alkaline solution, such as a sodium bicarbonate solution, or take an antacid preparation such as hydrated magnesium hydroxide (milk of magnesia) or calcium carbonate, which will raise the pH level in the stomach and cause rapid degradation of the enteric coupling polymers. The gastric residence system will then break apart and be eliminated from the patient. (Emphasis added.)
The linkers can be enteric linkers such as HPMCAS combined with PCL (0008 and 0009; emphasis added) or time dependent linkers (0007). The examiner considers the blend of HPMCAS and PCL to fall within the scope of “disintegrating matrix” recited in the instant claims, particularly in view of the instant specification, which states e.g. “some embodiments, the enteric disintegrating matrix comprises about 59 wt% to about 69 wt% HPMCAS, about 29 wt% to about 39 wt% PCL” (instant specification: 0109). The carrier polymer-agent (i.e. drug eluting segment) is preferably comprised of PCL and a drug (0217). The intercomponent anchors may be polycarbonate, polyphenylsulfone, a polyphenylene ether-polystyrene blend, polyphenylene ether, polystyrene, and polyether ether ketone (0012). These polymers also fall within the scope of the term “inert matrix”, as they are non-biodegradable (see Van Nest: 0087) Typically, when attaching two different elements, where each element comprises a common polymer, the common polymer is used as the interfacing polymer. For example, if a linker comprising 50% HPMCAS and 50% PCL is to be attached to a carrier polymer-therapeutic agent component comprising PCL and a drug, then PCL can be used as the interfacing polymer (0305).
Thus, Bellinger discloses a stellate gastroretentive drug delivery system comprising multi-segment arms formed from enteric matrices (disintegrating) or non-enteric matrices (inert) and teaches that the rate at which the enteric matrix segments degrade can be used to control the duration of time the system remains in the stomach before passing through the pyloric sphincter into the intestines allowing for drug elution from the carrier polymer-drug segments for a predetermined amount of time.
Bellinger ‘265 does not disclose an example gastroretentive system having the arrangement delineated in instant claims, 1, 2, 10, or 31.
Bellinger ‘966, describing a very similar gastrorententive dosage form (see: title, abstract, figures), teaches that use of multiple linker sections permits the gastric residence system to break into relatively small pieces after desired residence time for easier passage through the gastrointestinal tract (0090). Bellinger ‘966 teaches further advantages of multi-segment stellate gastroretentive systems including protection against undesired passage of the system into the small intestine, and easy removal if such is required prior to the designed residence time by consumption of an alkaline solution (0087). Bellinger also teaches that curved ends allow the system to fit more snugly into the capsule prior to administration (0097). Finally, Bellinger ‘966 teaches that the ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the system (abstract).
In view of the teachings set forth above, one having ordinary skill in the art would have understood that stellate gastroretentive systems can be designed to deliver risperidone with arms sufficiently long that the system does not pass out of the stomach, wherein the arms are comprised of multiple segments, some of which are degradable such that the arms break apart over time into pieces small enough to pass out of the stomach, where they are subsequently excreted, and that an additional curved cap segment would allow for longer arms, while permitting the folded system to fit snugly within a smaller capsule for easy swallowing.
Claims 1, 2, 10, and 31 are considered prima facie obvious, although the specific arrangement is not taught in a single embodiment or example, because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. Absent evidence of unexpectedly superior performance for the claimed arrangement of prior art segments within the arm, the examiner considers this to have been combining prior art elements according to known methods to yield predictable results (see MPEP 2143(I)(A)).
With regard to claims 33, 35, and 37, as noted above, the examiner finds the listed order to have been prima facie obvious because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. See MPEP 2143(I)(A).
With regard to claim 40, as noted above, Bellinger ‘265 discloses that the linkers can be time-dependent (0007).
With regard to claim 41, the ratio of HPMCAS to polycaprolactone in the linkers can be between about 80% HPMCAS:20% PCL to about 20% HPMCAS:80% PCL (0009). This range embraces the range recited in the instant claims. See MPEP 2144.05.
With regard to claim 46, as noted above the segments may be formed from PCL. Bellinger ‘265 also discloses that the segments may contain radiopaque substances such as bismuth subcarbonate (i.e. (BiO2)CO3; 0209).
With regard to claim 47, as noted above Bellinger ‘265 teaches enteric linkers (i.e. enteric disintegrating matrix).
With regard to claim 48, as noted above, Bellinger ‘265 teaches combining PCL with HPMCAS to form an enteric linker having optimized stability in the different regions of the gastrointestinal tract. Bellinger also teaches including poloxamers (i.e. PEG-PPG-PEG block copolymers) in the enteric linkers (0009).
With regard to claim 51, as discussed supra, Bellinger teaches that the carrier polymer-drug (i.e. drug-eluting) comprises PCL and can be formulated to deliver risperidone. This segment can also contain colloidal silicon dioxide (0230).
With regard to claim 52, as discussed in detail above, any segment of the stellate arms disclosed by Bellinger ‘265 may be formed from PCL.
With regard to claim 55, as discussed in the rejection of claim 57 above, it would have been prima facie obvious to coat the drug eluting segment because this results in nearly zero-order drug release, which would in turn provide constant plasma drug concentrations during the drug release period.
Claims 34 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Bellinger et al. (US 2019/0262265; publication date: 08/29/2019; cited in the IDS filed 09/15/2023), Kanasty et al. (Journal of Controlled Release vol 303 pages 34-41; publication year: 2019), and Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019), Van Nest (US 20010046967 Publication date 11/29/2001) and Bellinger (US 2019/0254966; publication date: 08/22/2019; cited in the IDS filed 09/15/2023) as applied to claims 1, 2, 10, 31, 33, 35, 37, 40, 41, 46-48, 51, 52, 55, 57, 82, and 90 above, and further in view of Reichenberger et al. (WO2019023346; publication date: 01/31/2019).
The relevant disclosures of Bellinger ‘265, Kanasty, Fitzpatrick, Van Nest, and Bellinger ‘966 are set forth above. None of these references disclose a stellate gastroretentive drug delivery system having at least one arm that excludes a drug eluting segment.
Reichenberger teaches that in stellate gastroretentive systems for drug delivery with arms that contain reservoirs of drug one or more arms may be composed of inert materials without drug present in the event that less drug needs to be delivered (0117 and 0118).
It would have been merely a matter of routine for one of ordinary skill to select the number of arms required to deliver risperidone in an amount to achieve a desired plasma concentration within the therapeutic window for this particular active agent. See MPEP 2144.05(II).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 57, 82, and 90 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-42 of U.S. Patent No. 10182985 (cited in the IDS filed 09/15/2023);
claims 1-13 of U.S. Patent No. 10532027 (cited in the IDS filed 09/15/2023);
claims 1-113 of U.S. Patent No. 10610482 (cited in the IDS filed 09/15/2023);
claims 1-74 of U.S. Patent No. 10517819 (cited in the IDS filed 09/15/2023);
claims 1-69 of U.S. Patent No. 10517820 (cited in the IDS filed 09/15/2023);
claims 1-45 of U.S. Patent No. 10596110 (cited in the IDS filed 09/15/2023);
claims 1-22 of U.S. Patent No. 10716752 (cited in the IDS filed 09/15/2023);
claims 1-40 of U.S. Patent No. 10716751 (cited in the IDS filed 09/15/2023);
claims 1-63 of U.S. Patent No. 11246829 (cited in the IDS filed 09/15/2023);
claims 1-47 of U.S. Patent No. 11077056 (cited in the IDS filed 09/15/2023);
claims 1-45 of U.S. Patent No. 11389399 (cited in the IDS filed 09/15/2023);
claims 1-42 of U.S. Patent No. 11357723 (cited in the IDS filed 09/15/2023);
claims 1-45 of U.S. Patent No. 11992552 (cited in the IDS filed 08/05/2024); and
claims 1-42 of U.S. Patent No. 12109305
in view of in view of Kanasty et al. (Journal of Controlled Release vol 303 pages 34-41; publication year: 2019) and further in view of Bellinger et al. (US 2019/0262265; publication date: 08/29/2019) and Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019).
Inter alia, the claims of the patents embrace a gastric residence structure having an elastic central component to which are affixed multiple arms in a stellate arrangement (i.e. such that the arm comprises a proximal end, a distal end, and an outer surface therebetween; wherein the proximal end of each arm is attached to the central component and projects radially from the elastomer component, each arm having its distal end not attached to the central component and located at a larger radial distance from the elastomer component than the proximal end). The central component is expressly recited to be an elastomeric component or described as “the system is configured to be folded and physically constrained during administration and is configured to assume an open retention shape upon removal of a constraint, wherein change between the folded shape and the open retention shape is mediated by the second polymeric component that undergoes elastic deformation when the residence system is in the folded shape and recoils when the gastric residence system assumes the open retention shape” (i.e. the central polymeric component is an elastomer that mediates folding of the system). The arms contain linkers joining segments of the arms. The polymeric components include an active agent and a polymer (i.e. the arms comprise a drug eluting segment comprising a carrier polymer and a drug, which may be risperidone; see specification of the ‘985, ‘027, and ‘482 patents, which indicate that the “active substance” may be risperidone).
The range in number of arms required by the patent overlaps with the number of arms required by the instant claims. See MPEP 2144.05.
The cited patents do not recite a limitation requiring the drug eluting segment to be coated.
Kanasty discloses a stellate gastroretentive dosage form (figure 1, page 35) wherein coating the drug releasing polymer matrix leads to near linear drug release for a memantine formulation (abstract, title, figure 1, and figure 3). The coating is formed from a polymer (section 4.1, page 40), which as can be seen from figure 3 modulates the release rate of the drug from the polymer matrix.
It would have been prima facie obvious to coat the drug eluting segment with a release rate modulating polymer film. The skilled artisan would have been motivated to do so in order to provide steady consistent release of drug, and in turn consistent plasma profiles, after administration. The skilled artisan would have had a reasonable expectation of success because this had been achieved with a different drug, as demonstrated by Kanasty.
Moreover, Kanasty teaches the instantly claimed design of a stellate gastroretentive system to be highly effective for maintaining the system in the stomach during an extended drug delivery period followed by disintegration and excretion at a designated time. It would have been obvious to select the 6-armed stellate design of Kanasty from the broader limitations of the cited patents because such was known to be optimal for retention in the stomach as of the instant effective filing date.
The claims also do not disclose a filament circumferentially connecting each arm.
Bellinger discloses that there may be webbing between the arms of stellate gastroretentive dosage forms (figure 35). The webbing can present to varying extents (figure 35A-D) and provides “resistance to x-y bending than the unwebbed designs; as the amount of webbing is increased, the x-y bending force increases” (0191). Bellinger discloses further a relationship between “[r]esistance to x-y bending and “amount of webbing between elastomer arms” and also with the durometer of the central elastomer asterisk member (0192). Designing the system to have optimal x-y bending force such that it can be folded into a capsule but remails extended once it has expanded in the stomach is essential for delivery and retention in the stomach for the intended duration (0190). One having ordinary skill in the art would have recognized that the web in Bellinger’s invention connects the arms, contributing to holding them in place once the device has expanded in the stomach.
Fitzpatrick, in the analogous art of gastroretentive dosage forms (page 1), discloses some physical linkages that may connect elements of a gastroretentive device, such as fibrous materials including suture material or threads (page 8).
It would have been prima facie obvious to connect the arms of the stellate gastroretentive dosage form embraced by the patents using a thread or string (which the examiner considers to fall within the scope of the term “filament” recited in the instant claims) in place of the of the webbing because one of ordinary skill would have recognized it to serve the same purpose of holding the structure in the desired conformation. See MPEP 2143(I)(B).
Claims 82 and 90 require various pharmacodynamic properties of the formulation for risperidone delivery, in the alternative. The examiner considers optimizing risperidone release to have been a matter of routine testing for one of ordinary skill within the parameters of the cited patents and prior art on how to achieve steady state extended release of any drug, including risperidone, and for this reason the examiner does not consider the functional language of claims 82 and 90 to patentably define over the cited prior art.
Claims 1, 2, 10, 31, 33, 35, 37, 40, 41, 46-48, 51, 52, and 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-42 of U.S. Patent No. 10182985 (cited in the IDS filed 09/15/2023);
claims 1-13 of U.S. Patent No. 10532027 (cited in the IDS filed 09/15/2023);
claims 1-113 of U.S. Patent No. 10610482 (cited in the IDS filed 09/15/2023);
claims 1-74 of U.S. Patent No. 10517819 (cited in the IDS filed 09/15/2023);
claims 1-69 of U.S. Patent No. 10517820 (cited in the IDS filed 09/15/2023);
claims 1-45 of U.S. Patent No. 10596110 (cited in the IDS filed 09/15/2023);
claims 1-22 of U.S. Patent No. 10716752 (cited in the IDS filed 09/15/2023);
claims 1-40 of U.S. Patent No. 10716751 (cited in the IDS filed 09/15/2023);
claims 1-63 of U.S. Patent No. 11246829 (cited in the IDS filed 09/15/2023);
claims 1-47 of U.S. Patent No. 11077056 (cited in the IDS filed 09/15/2023);
claims 1-45 of U.S. Patent No. 11389399 (cited in the IDS filed 09/15/2023);
claims 1-42 of U.S. Patent No. 11357723 (cited in the IDS filed 09/15/2023);
claims 1-45 of U.S. Patent No. 11992552 (cited in the IDS filed 08/05/2024); and
claims 1-42 of U.S. Patent No. 12109305
in view of in view of Kanasty et al. (Journal of Controlled Release vol 303 pages 34-41; publication year: 2019), Bellinger et al. (US 2019/0262265; publication date: 08/29/2019) and Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019) as applied to claims 57, 82, and 90 above, and further in view of Van Nest (US 20010046967 Publication date 11/29/2001) and Bellinger (US 2019/0254966; publication date: 08/22/2019).
The relevant limitations of the cited patents and teachings of Bellinger ‘265, Kanasty, and Fitzpatrick are set forth above and render obvious a gastric residence system comprising: at least three arms affixed to a central elastomer, wherein at least one arm comprises a drug-eluting segment, each arm comprising a proximal end, a distal end, and an outer surface therebetween; wherein the proximal end of each arm is attached to the elastomer component and projects radially from the elastomer component, each arm having its distal end not attached to the elastomer component and located at a larger radial distance from the elastomer component than the proximal end; wherein the drug eluting segment comprises a carrier polymer, and risperidone or a salt thereof; wherein the drug eluting segment further comprises a coating comprising a release rate- modulating polymer film; and a filament circumferentially connecting each arm.
The cited patents do not teach the specific arrangement of segments required by the instant claims.
Bellinger discloses further that the arms can be comprised of “at least two segments” (0063), thus Bellinger discloses arms comprising multiple segments. The segments are adhered together by “coupling polymers”, which are polymers suitable for coupling other polymers together (0145). The arms can contain an anchor segment, a linker segment, a interfacing polymer segment, and a carrier polymer-drug segment (0007 and 0008). The various segments are formed from polymers that control their dissolution in different portions of the gastrointestinal tract; in para 0165, Bellinger discloses further:
The gastric residence system passes out of the stomach at an appropriate time point, that is, once the useful therapeutic agent delivery lifetime of the system has been reached, or at a reasonable fraction of the useful therapeutic agent delivery lifetime of the system. This is accomplished by suitable choice of the coupling polymer components and the dimensions of the system. In its intact, uncompressed form, the gastric residence system is designed to resist passage through the pyloric sphincter. That is, in its intact form, the gastric residence system is too large to pass through the pyloric sphincter. The coupling polymer components are chosen such that they gradually weaken and/or degrade over the residence period in the stomach. When the coupling polymer components are sufficiently weakened or degraded, the gastric residence system breaks apart into smaller pieces, which are able to pass through the pyloric sphincter. The system then passes through the intestines and is eliminated from the patient. (Emphasis added.)
In para 0167, Bellinger discloses:
In its desired mode of operation, the gastric residence systems have their intact uncompressed form while resident in the stomach, and do not pass through the pylorus until they break apart after the desired residence time. If a gastric residence system passes intact into the intestine, it has the potential to result in intestinal blockage. Thus, the gastric residence systems are designed to uncouple rapidly in the intestinal environment by dissolution of the coupling polymer, within 48 hours, preferably within 24 hours, more preferably within 12 hours, yet more preferably within 1-2 hours, so as to avoid potential intestinal blockage. This is readily accomplished by using enteric polymers as the coupling polymers. Enteric polymers are relatively resistant to the acidic pH levels encountered in the stomach, but dissolve rapidly at the higher pH levels found in the duodenum. Use of enteric coupling polymers as safety elements protects against undesired passage of the intact gastric residence system into the small intestine. The use of enteric coupling polymers also provides a manner of removing the gastric residence system prior to its designed residence time; should the system need to be removed, the patient can drink a mildly alkaline solution, such as a sodium bicarbonate solution, or take an antacid preparation such as hydrated magnesium hydroxide (milk of magnesia) or calcium carbonate, which will raise the pH level in the stomach and cause rapid degradation of the enteric coupling polymers. The gastric residence system will then break apart and be eliminated from the patient. (Emphasis added.)
The linkers can be enteric linkers such as HPMCAS combined with PCL (0008 and 0009; emphasis added) or time dependent linkers (0007). The examiner considers the blend of HPMCAS and PCL to fall within the scope of “disintegrating matrix” recited in the instant claims, particularly in view of the instant specification, which states e.g. “some embodiments, the enteric disintegrating matrix comprises about 59 wt% to about 69 wt% HPMCAS, about 29 wt% to about 39 wt% PCL” (instant specification: 0109). The carrier polymer-agent (i.e. drug eluting segment) is preferably comprised of PCL and a drug (0217). The intercomponent anchors may be polycarbonate, polyphenylsulfone, a polyphenylene ether-polystyrene blend, polyphenylene ether, polystyrene, and polyether ether ketone (0012). These polymers also fall within the scope of the term “inert matrix”, as they are non-biodegradable (see Van Nest: 0087) Typically, when attaching two different elements, where each element comprises a common polymer, the common polymer is used as the interfacing polymer. For example, if a linker comprising 50% HPMCAS and 50% PCL is to be attached to a carrier polymer-therapeutic agent component comprising PCL and a drug, then PCL can be used as the interfacing polymer (0305).
Thus, Bellinger discloses a stellate gastroretentive drug delivery system comprising multi-segment arms formed from enteric matrices (disintegrating) or non-enteric matrices (inert) and teaches that the rate at which the enteric matrix segments degrade can be used to control the duration of time the system remains in the stomach before passing through the pyloric sphincter into the intestines allowing for drug elution from the carrier polymer-drug segments for a predetermined amount of time.
Bellinger ‘966, describing a very similar gastrorententive dosage form (see: title, abstract, figures), teaches that use of multiple linker sections permits the gastric residence system to break into relatively small pieces after desired residence time for easier passage through the gastrointestinal tract (0090). Bellinger ‘966 teaches further advantages of multi-segment stellate gastroretentive systems including protection against undesired passage of the system into the small intestine, and easy removal if such is required prior to the designed residence time by consumption of an alkaline solution (0087). Bellinger also teaches that curved ends allow the system to fit more snugly into the capsule prior to administration (0097). Finally, Bellinger ‘966 teaches that the ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the system (abstract).
In view of the teachings set forth above, one having ordinary skill in the art would have understood that stellate gastroretentive systems can be designed to deliver risperidone with arms sufficiently long that the system does not pass out of the stomach, wherein the arms are comprised of multiple segments, some of which are degradable such that the arms break apart over time into pieces small enough to pass out of the stomach, where they are subsequently excreted, and that an additional curved cap segment would allow for longer arms, while permitting the folded system to fit snugly within a smaller capsule for easy swallowing.
Claims 1, 2, 10, and 31 are considered prima facie obvious, although the specific arrangement is not taught in a single embodiment or example, because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. Absent evidence of unexpectedly superior performance for the claimed arrangement of prior art segments within the arm, the examiner considers this to have been combining prior art elements according to known methods to yield predictable results (see MPEP 2143(I)(A)).
With regard to claims 33, 35, and 37, as noted above, the examiner finds the listed order to have been prima facie obvious because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. See MPEP 2143(I)(A).
With regard to claim 40, as noted above, Bellinger ‘265 discloses that the linkers can be time-dependent (0007).
With regard to claim 41, the ratio of HPMCAS to polycaprolactone in the linkers can be between about 80% HPMCAS:20% PCL to about 20% HPMCAS:80% PCL (0009). This range embraces the range recited in the instant claims. See MPEP 2144.05.
With regard to claim 46, as noted above the segments may be formed from PCL. Bellinger ‘265 also discloses that the segments may contain radiopaque substances such as bismuth subcarbonate (i.e. (BiO2)CO3; 0209).
With regard to claim 47, as noted above Bellinger ‘265 teaches enteric linkers (i.e. enteric disintegrating matrix).
With regard to claim 48, as noted above, Bellinger ‘265 teaches combining PCL with HPMCAS to form an enteric linker having optimized stability in the different regions of the gastrointestinal tract. Bellinger also teaches including poloxamers (i.e. PEG-PPG-PEG block copolymers) in the enteric linkers (0009).
With regard to claim 51, as discussed supra, Bellinger teaches that the carrier polymer-drug (i.e. drug-eluting) comprises PCL and can be formulated to deliver risperidone. This segment can also contain colloidal silicon dioxide (0230).
With regard to claim 52, as discussed in detail above, any segment of the stellate arms disclosed by Bellinger ‘265 may be formed from PCL.
With regard to claim 55, as discussed in the rejection of claim 57 above, it would have been prima facie obvious to coat the drug eluting segment because this results in nearly zero-order drug release, which would in turn provide constant plasma drug concentrations during the drug release period.
Claims 34 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-42 of U.S. Patent No. 10182985 (cited in the IDS filed 09/15/2023);
claims 1-13 of U.S. Patent No. 10532027 (cited in the IDS filed 09/15/2023);
claims 1-113 of U.S. Patent No. 10610482 (cited in the IDS filed 09/15/2023);
claims 1-74 of U.S. Patent No. 10517819 (cited in the IDS filed 09/15/2023);
claims 1-69 of U.S. Patent No. 10517820 (cited in the IDS filed 09/15/2023);
claims 1-45 of U.S. Patent No. 10596110 (cited in the IDS filed 09/15/2023);
claims 1-22 of U.S. Patent No. 10716752 (cited in the IDS filed 09/15/2023);
claims 1-40 of U.S. Patent No. 10716751 (cited in the IDS filed 09/15/2023);
claims 1-63 of U.S. Patent No. 11246829 (cited in the IDS filed 09/15/2023);
claims 1-47 of U.S. Patent No. 11077056 (cited in the IDS filed 09/15/2023);
claims 1-45 of U.S. Patent No. 11389399 (cited in the IDS filed 09/15/2023);
claims 1-42 of U.S. Patent No. 11357723 (cited in the IDS filed 09/15/2023);
claims 1-45 of U.S. Patent No. 11992552 (cited in the IDS filed 08/05/2024); and
claims 1-42 of U.S. Patent No. 12109305
in view of in view of Kanasty et al. (Journal of Controlled Release vol 303 pages 34-41; publication year: 2019), Bellinger et al. (US 2019/0262265; publication date: 08/29/2019), Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019) Van Nest (US 20010046967 Publication date 11/29/2001), and Bellinger (US 2019/0254966; publication date: 08/22/2019) as applied to claims 1, 2, 10, 31, 33, 35, 37, 40, 41, 46-48, 51, 52, 55, 57, 82, and 90 above, and further in view of Reichenberger et al. (WO2019/023346; publication date: 01/31/2019).
The relevant limitations of the cited patents and disclosures of Bellinger ‘265, Kanasty, Fitzpatrick, Van Nest, and Bellinger ‘966 are set forth above. None of these references disclose a stellate gastroretentive drug delivery system having at least one arm that excludes a drug eluting segment.
Reichenberger teaches that in stellate gastroretentive systems for drug delivery with arms that contain reservoirs of drug one or more arms may be composed of inert materials without drug present in the event that less drug needs to be delivered (0117 and 0118).
It would have been merely a matter of routine for one of ordinary skill to select the number of arms required to deliver risperidone in an amount to achieve a desired plasma concentration within the therapeutic window for this particular active agent. See MPEP 2144.05(II).
Claims 1, 2, 10, 31, 33-35, 37, 38, 40, 41, 46-48, 51, 52, 55, 57, 82, and 90 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11576866 (cited in the IDS filed 09/15/2023) in view of Bellinger (US 2019/0254966; publication date: 08/22/2019) and Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019).
Inter alia the claims of the patent embrace a stellate gastric residence system comprising: wherein the gastric residence system comprises a plurality of a plurality of elongate members affixed to a central elastomer, wherein at least one elongate member comprises: a carrier polymer, a drug, a release rate-modulating polymer film coated on the surface of the at least one elongate member, wherein the elongate members are affixed to the central elastomer via linkers, wherein the linkers are configured to weaken or degrade to allow passage of the gastric residence system through a pylorus after the specified gastric residence period.
The claims of the patent do not require the gastric residence system to contain risperidone, but rather an adamantane class drug.
Bellinger discloses a nearly identical stellate gastroretentive system for extended drug delivery to the stomach and indicates that the drug may be risperidone or the system can be formulated to deliver a multitude of active agents other than risperidone (0196).
The claims of the patent are considered an obvious variant of the instant claims because, in view of the prior art, the inventive elements relate to the gastroretentive structure itself rather than the particular agent being delivered.
The issued patent does not require a filament circumferentially connecting each arm.
Fitzpatrick, in the analogous art of gastroretentive dosage forms (page 1), discloses some physical linkages that may connect elements of a gastroretentive device, such as fibrous materials including suture material or threads (page 8).
It would have been prima facie obvious to connect the arms of the stellate gastroretentive dosage form embraced by the issued patent using a thread or string (which the examiner considers to fall within the scope of the term “filament” recited in the instant claims) in place of the of the webbing because one of ordinary skill would have recognized it to serve the same purpose of holding the structure in the desired conformation. See MPEP 2143(I)(B).
The claims of the issued patent do not describe the number and location of segments within the arms/elongate members of the stellate system having the arrangement of instant claims 1, 2, 10, and 31.
Bellinger ‘966, describing a very similar gastrorententive dosage form (see: title, abstract, figures), teaches that use of multiple linker sections permits the gastric residence system to break into relatively small pieces after desired residence time for easier passage through the gastrointestinal tract (0090). Bellinger ‘966 teaches further advantages of multi-segment stellate gastroretentive systems including protection against undesired passage of the system into the small intestine, and easy removal if such is required prior to the designed residence time by consumption of an alkaline solution (0087). Bellinger also teaches that curved ends allow the system to fit more snugly into the capsule prior to administration (0097). Finally, Bellinger ‘966 teaches that the ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the system (abstract).
In view of the teachings set forth above, one having ordinary skill in the art would have understood that stellate gastroretentive systems can be designed to deliver risperidone with arms sufficiently long that the system does not pass out of the stomach, wherein the arms are comprised of multiple segments, some of which are degradable such that the arms break apart over time into pieces small enough to pass out of the stomach, where they are subsequently excreted, and that an additional curved cap segment would allow for longer arms, while permitting the folded system to fit snugly within a smaller capsule for easy swallowing.
Claims 1, 2, 10, and 31 as well as claims 33, 35, and 37 are considered prima facie obvious, although the specific arrangement is not recited in the issued patent, because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. Absent evidence of unexpectedly superior performance for the claimed arrangement of prior art segments within the arm, the examiner considers this to have been combining prior art elements according to known methods to yield predictable results (see MPEP 2143(I)(A)).
With regard to claim 40, as noted above, Bellinger discloses that the linkers can be time-dependent (0110).
With regard to claim 41, Bellinger discloses forming segments from HPMCAS (0157 or PCL (0122) in a variety of rations (0184) and it would have been prima facie obvious to one of ordinary skill to optimize dissolution of the segments based on quantity of each polymer. See MPEP 2144.05.
With regard to claim 46, as noted above the segments may be formed from PCL. Bellinger also discloses that the segments may contain radiopaque substances such as bismuth subcarbonate (i.e. (BiO2)CO3; 0209).
With regard to claim 47, as noted above Bellinger teaches enteric linkers (i.e. enteric disintegrating matrix).
With regard to claim 48, as noted above, Bellinger teaches combining PCL with HPMCAS to form an enteric linker having optimized stability in the different regions of the gastrointestinal tract. Bellinger also teaches including poloxamers (i.e. PEG-PPG-PEG block copolymers) in the enteric linkers (e.g. claim 9).
With regard to claim 51, as discussed supra, Bellinger teaches that the carrier polymer-drug (i.e. drug-eluting) comprises PCL and can be formulated to deliver risperidone. This segment can also contain colloidal silicon dioxide (0170).
With regard to claim 52, as discussed in detail above, any segment of the stellate arms disclosed by Bellinger may be formed from PCL.
Claims 82 and 90 require various pharmacodynamic properties of the formulation for risperidone delivery, in the alternative. The examiner considers optimizing risperidone release to have been a matter of routine testing for one of ordinary skill in view of the teachings provided by Bellinger on how to achieve steady state extended release of any drug, including risperidone, and for this reason the examiner does not consider the functional language of claims 82 and 90 to patentably define over the cited prior art.
Claims 57, 82, and 90 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-57 of U.S. Patent No. 12023406 (cited in the IDS filed 09/15/2023) in view of Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019).
Inter alia, the claims of the issued patent embrace a gastric residence system to deliver risperidone comprising a therapeutically effective amount of an agent or a pharmaceutically acceptable salt thereof, wherein: the gastric residence system has a compacted configuration and an uncompacted configuration, the gastric residence system comprises a plurality of elongate members affixed to a central elastomer, wherein at least one elongate member comprises: a carrier polymer, the agent or the pharmaceutically acceptable salt thereof, and a release-rate modulating polymer film coated on the surface of the at least one elongate member, wherein the elongate members are affixed to the central elastomer via linkers, wherein the linkers are configured to weaken or degrade to allow passage of the gastric residence system through the pylorus after the specified gastric residence period. At least one elongate member comprises at least two segments joined by linkers, wherein the linkers are configured to weaken or degrade to allow passage of the gastric residence system through the pylorus after the specified gastric residence period.
The claims do not require a filament circumferentially connecting each arm.
Fitzpatrick, in the analogous art of gastroretentive dosage forms (page 1), discloses some physical linkages that may connect elements of a gastroretentive device, such as fibrous materials including suture material or threads (page 8).
It would have been prima facie obvious to connect the arms of the stellate gastroretentive dosage form embraced by the patent using a thread or string (which the examiner considers to fall within the scope of the term “filament” recited in the instant claims) in place of the of the webbing because one of ordinary skill would have recognized it to serve the same purpose of holding the structure in the desired conformation. See MPEP 2143(I)(B).
Claims 82 and 90 require various pharmacodynamic properties of the formulation for risperidone delivery, in the alternative. The examiner considers optimizing risperidone release to have been a matter of routine testing for one of ordinary skill within the parameters of the cited patents and prior art on how to achieve steady state extended release of any drug, including risperidone, and for this reason the examiner does not consider the functional language of claims 82 and 90 to patentably define over the cited prior art.
Claims 1, 2, 10, 31, 33-35, 37, 38, 40, 41, 46-48, 51, 52, and 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-57 of U.S. Patent No. 12023406 (cited in the IDS filed 09/15/2023) in view of Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019) as applied to claims 57, 82, and 90 above, and further in view of Bellinger (US 2019/0254966; publication date: 08/22/2019).
The relevant limitations of the cited patent and teachings Fitzpatrick are set forth above and render obvious a gastric residence system comprising: at least three arms affixed to a central elastomer, wherein at least one arm comprises a drug-eluting segment, each arm comprising a proximal end, a distal end, and an outer surface therebetween; wherein the proximal end of each arm is attached to the elastomer component and projects radially from the elastomer component, each arm having its distal end not attached to the elastomer component and located at a larger radial distance from the elastomer component than the proximal end; wherein the drug eluting segment comprises a carrier polymer, and risperidone or a salt thereof; wherein the drug eluting segment further comprises a coating comprising a release rate- modulating polymer film; and a filament circumferentially connecting each arm.
The claims of the issued patent do not describe the number and location of segments within the arms/elongate members of the stellate system having the arrangement of instant claims 1, 2, 10, and 31.
Bellinger ‘966, describing a very similar gastroretentive dosage form (see: title, abstract, figures), teaches that use of multiple linker sections permits the gastric residence system to break into relatively small pieces after desired residence time for easier passage through the gastrointestinal tract (0090). Bellinger ‘966 teaches further advantages of multi-segment stellate gastroretentive systems including protection against undesired passage of the system into the small intestine, and easy removal if such is required prior to the designed residence time by consumption of an alkaline solution (0087). Bellinger also teaches that curved ends allow the system to fit more snugly into the capsule prior to administration (0097). Finally, Bellinger ‘966 teaches that the ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the system (abstract).
In view of the teachings set forth above, one having ordinary skill in the art would have understood that stellate gastroretentive systems can be designed to deliver risperidone with arms sufficiently long that the system does not pass out of the stomach, wherein the arms are comprised of multiple segments, some of which are degradable such that the arms break apart over time into pieces small enough to pass out of the stomach, where they are subsequently excreted, and that an additional curved cap segment would allow for longer arms, while permitting the folded system to fit snugly within a smaller capsule for easy swallowing.
Claims 1, 2, 10, and 31 as well as claims 33, 35, and 37 are considered prima facie obvious, although the specific arrangement is not recited in the issued patent, because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. Absent evidence of unexpectedly superior performance for the claimed arrangement of prior art segments within the arm, the examiner considers this to have been combining prior art elements according to known methods to yield predictable results (see MPEP 2143(I)(A)).
With regard to claim 40, as noted above, Bellinger discloses that the linkers can be time-dependent (0110).
With regard to claim 41, Bellinger discloses forming segments from HPMCAS (0157 or PCL (0122) in a variety of rations (0184) and it would have been prima facie obvious to one of ordinary skill to optimize dissolution of the segments based on quantity of each polymer. See MPEP 2144.05.
With regard to claim 46, as noted above the segments may be formed from PCL. Bellinger also discloses that the segments may contain radiopaque substances such as bismuth subcarbonate (i.e. (BiO2)CO3; 0209).
With regard to claim 47, as noted above Bellinger teaches enteric linkers (i.e. enteric disintegrating matrix).
With regard to claim 48, as noted above, Bellinger teaches combining PCL with HPMCAS to form an enteric linker having optimized stability in the different regions of the gastrointestinal tract. Bellinger also teaches including poloxamers (i.e. PEG-PPG-PEG block copolymers) in the enteric linkers (e.g. claim 9).
With regard to claim 51, as discussed supra, Bellinger teaches that the carrier polymer-drug (i.e. drug-eluting) comprises PCL and can be formulated to deliver risperidone. This segment can also contain colloidal silicon dioxide (0170).
With regard to claim 52, as discussed in detail above, any segment of the stellate arms disclosed by Bellinger may be formed from PCL.
With regard to claim 55, as discussed in the rejection of claim 57 above, it would have been prima facie obvious to coat the drug eluting segment because this results in nearly zero-order drug release, which would in turn provide constant plasma drug concentrations during the drug release period.
Claims 1, 2, 10, 31, 33-35, 37, 38, 40, 41, 46-48, 51, 52, 55, 57, 82, and 90 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 10, 31, 33-35, 37, 38, 40, 41, 46-48, 51, 52, 55, 57, 70, and 80 of copending Application No. 18729705 in view of Bellinger et al. (US 2019/0262265; publication date: 08/29/2019).
The claims of the copending application are identical to the instant claims except that the copending application recites a limitation requiring the agent not to be risperidone, whereas the instant claims require risperidone.
Bellinger discloses a nearly identical stellate gastroretentive system for extended drug delivery to the stomach and indicates that the drug may be risperidone or the system can be formulated to deliver a multitude of active agents other than risperidone (0270).
The claims of the copending application are considered an obvious variant of the instant claims because, in view of the prior art, the inventive elements relate to the gastroretentive structure itself rather than the particular agent being delivered.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 10, 31, 33-35, 37, 38, 40, 41, 46-48, 51, 52, 55, 57, 82, and 90 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-19, 36, 40, 41, 63, 64, 68-74, 97, 101, and 102 of copending Application No. 18289331 in view of Bellinger et al. (US 2019/0262265; publication date: 08/29/2019).
Inter alia, the claims of the copending application embrace a stellate gastroretentive dosage form for drug delivery comprising: a plurality of arms affixed to a central elastomer, wherein at least one arm comprises a drug-eluting component; each arm comprising a proximal end, a distal end, and an outer surface therebetween; wherein the proximal end of each arm is attached to the elastomer component and projects radially from the elastomer component, each arm having its distal end not attached to the elastomer component and located at a larger radial distance from the elastomer component than the proximal end; wherein the at least one arm comprising a drug eluting component comprises: a polymeric linker segment; a first disintegrating matrix segment attached to the polymeric linker segment; a first inert segment attached to the first disintegrating matrix segment; a second disintegrating matrix segment attached to the first inert segment; a second inert segment attached to the second disintegrating matrix segment ;the drug-eluting component attached to the second inert segment, wherein the drug eluting component comprises a carrier polymer, buprenorphine or a salt thereof, and naloxone or a salt thereof, and wherein the drug eluting component further comprises a coating comprising a release rate-modulating polymer film; a third inert segment attached to the drug-eluting component; a third disintegrating matrix segment attached to the third inert segment; and a filament circumferentially connecting each arm. The active agent may be present in less than all of the arms.
The scope of the structural elements falls within or overlaps with the scope of the structural elements recited in instant claims 1, 2, 10, 31, and 57.
The claims of the copending application differ from the instant claims in that the drug to be delivered is buprenorphine and naloxone, whereas the instant claims require risperidone.
Bellinger discloses a nearly identical stellate gastroretentive system for extended drug delivery to the stomach and indicates that the drug may be risperidone or the system can be formulated to deliver a multitude of active agents other than risperidone (0270).
The claims of the copending application are considered an obvious variant of the instant claims because, in view of the prior art, the inventive elements relate to the gastroretentive structure itself rather than the particular agent being delivered.
Regarding the instant dependent claims, Bellinger provides further guidance as to structural design of the segments, linkers, and arms/elongate members:
With regard to claim 40, as noted above, Bellinger ‘265 discloses that the linkers can be time-dependent (0007).
With regard to claim 41, the ratio of HPMCAS to polycaprolactone in the linkers can be between about 80% HPMCAS:20% PCL to about 20% HPMCAS:80% PCL (0009). This range embraces the range recited in the instant claims. See MPEP 2144.05.
With regard to claim 46, as noted above the segments may be formed from PCL. Bellinger ‘265 also discloses that the segments may contain radiopaque substances such as bismuth subcarbonate (i.e. (BiO2)CO3; 0209).
With regard to claim 47, as noted above Bellinger ‘265 teaches enteric linkers (i.e. enteric disintegrating matrix).
With regard to claim 48, as noted above, Bellinger ‘265 teaches combining PCL with HPMCAS to form an enteric linker having optimized stability in the different regions of the gastrointestinal tract. Bellinger also teaches including poloxamers (i.e. PEG-PPG-PEG block copolymers) in the enteric linkers (0009).
With regard to claim 51, as discussed supra, Bellinger teaches that the carrier polymer-drug (i.e. drug-eluting) comprises PCL and can be formulated to deliver risperidone. This segment can also contain colloidal silicon dioxide (0230).
With regard to claim 52, as discussed in detail above, any segment of the stellate arms disclosed by Bellinger ‘265 may be formed from PCL.
It would have been prima facie obvious to follow the specific formulation guidance provided by Bellinger to manufacture the stellate gastroretentive dosage form of the copending application because this would have been merely combining prior art elements according to known methods to yield predictable results (see MPEP 2143(I)(A)).
Claims 82 and 90 require various pharmacodynamic properties of the formulation for risperidone delivery, in the alternative. The examiner considers optimizing risperidone release to have been a matter of routine testing for one of ordinary skill in view of the teachings provided by Bellinger on how to achieve steady state extended release of any drug, including risperidone, and for this reason the examiner does not consider the functional language of claims 82 and 90 to patentably define over the cited prior art.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 10, 31, 33-35, 37, 38, 40, 41, 46-48, 51, 52, 55, 57, 82, and 90 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1, 2, 5, 7, 8, 10, 11, 13, 14, 17, 20, 22-24, 29, 31-33, 35, and 70 of copending Application No. 17774126;
claims 1, 2, 5-10, 12, 14-17, 19, 20, 24, 26, 28, and 30 of copending Application No. 17774445; and
claims 1-14 and 25-30 of copending Application No. 19082659
in view of Bellinger (US 2019/0254966; publication date: 08/22/2019) and Kanasty et al. (Journal of Controlled Release vol 303 pages 34-41; publication year: 2019).
Inter alia the claims of the copending applications embrace a gastric residence system comprising: one or more arms extending radially, wherein the one or more arms comprises a first segment comprising a first polymer composition and a second segment comprising a second polymer composition, a core, and a core and a plurality of arms connected to the core and extending radially from the core, i.e. a stellate gastric retentive system. The arms contain segments within them. The system contains a filament circumferentially connecting each arm of the plurality of arms.
The claims of the copending applications do not require the gastric residence system to contain risperidone.
Bellinger discloses a nearly identical stellate gastroretentive system for extended drug delivery to the stomach and indicates that the drug may be risperidone or the system can be formulated to deliver a multitude of active agents other than risperidone (0196).
The claims of the copending application are considered an obvious variant of the instant claims because, in view of the prior art, the inventive elements relate to the gastroretentive structure itself rather than the particular agent being delivered.
The copending applications do not expressly require a coating over the drug eluting segment comprising a release rate-modulating polymer film.
Kanasty discloses a stellate gastroretentive dosage form (figure 1, page 35) wherein coating the drug releasing polymer matrix leads to near linear drug release for a memantine formulation (abstract, title, figure 1, and figure 3). The coating is formed from a polymer (section 4.1, page 40), which as can be seen from figure 3 modulates the release rate of the drug from the polymer matrix.
It would have been prima facie obvious to coat the drug eluting segment with a release rate modulating polymer film. The skilled artisan would have been motivated to do so in order to provide steady consistent release of drug, and in turn consistent plasma profiles, after administration. The skilled artisan would have had a reasonable expectation of success because this had been achieved with a different drug, as demonstrated by Kanasty.
The claims of the ‘659 application recite further detail regarding the arrangement of the arms and segments within in a manner identical to or falling within the scope of instant claims 1, 2, 10, 31, and 57.
The claims of the ‘126 and ‘445 applications do not describe the number and location of segments within the arms/elongate members of the stellate system having the arrangement of instant claims 1, 2, 10, and 31.
Bellinger ‘966, describing a very similar gastrorententive dosage form (see: title, abstract, figures), teaches that use of multiple linker sections permits the gastric residence system to break into relatively small pieces after desired residence time for easier passage through the gastrointestinal tract (0090). Bellinger ‘966 teaches further advantages of multi-segment stellate gastroretentive systems including protection against undesired passage of the system into the small intestine, and easy removal if such is required prior to the designed residence time by consumption of an alkaline solution (0087). Bellinger also teaches that curved ends allow the system to fit more snugly into the capsule prior to administration (0097). Finally, Bellinger ‘966 teaches that the ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the system (abstract).
In view of the teachings set forth above, one having ordinary skill in the art would have understood that stellate gastroretentive systems can be designed to deliver risperidone with arms sufficiently long that the system does not pass out of the stomach, wherein the arms are comprised of multiple segments, some of which are degradable such that the arms break apart over time into pieces small enough to pass out of the stomach, where they are subsequently excreted, and that an additional curved cap segment would allow for longer arms, while permitting the folded system to fit snugly within a smaller capsule for easy swallowing.
Claims 1, 2, 10, and 31 as well as claims 33, 35, and 37 are considered prima facie obvious, although the specific arrangement is not recited in the ‘126 and ‘445 applications, because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. Absent evidence of unexpectedly superior performance for the claimed arrangement of prior art segments within the arm, the examiner considers this to have been combining prior art elements according to known methods to yield predictable results (see MPEP 2143(I)(A)).
With regard to claim 40, as noted above, Bellinger discloses that the linkers can be time-dependent (0110).
With regard to claim 41, Bellinger discloses forming segments from HPMCAS (0157 or PCL (0122) in a variety of rations (0184) and it would have been prima facie obvious to one of ordinary skill to optimize dissolution of the segments based on quantity of each polymer. See MPEP 2144.05.
With regard to claim 46, as noted above the segments may be formed from PCL. Bellinger also discloses that the segments may contain radiopaque substances such as bismuth subcarbonate (i.e. (BiO2)CO3; 0209).
With regard to claim 47, as noted above Bellinger teaches enteric linkers (i.e. enteric disintegrating matrix).
With regard to claim 48, as noted above, Bellinger teaches combining PCL with HPMCAS to form an enteric linker having optimized stability in the different regions of the gastrointestinal tract. Bellinger also teaches including poloxamers (i.e. PEG-PPG-PEG block copolymers) in the enteric linkers (e.g. claim 9).
With regard to claim 51, as discussed supra, Bellinger teaches that the carrier polymer-drug (i.e. drug-eluting) comprises PCL and can be formulated to deliver risperidone. This segment can also contain colloidal silicon dioxide (0170).
With regard to claim 52, as discussed in detail above, any segment of the stellate arms disclosed by Bellinger may be formed from PCL.
With regard to claim 55, as discussed in the rejection of claim 57 above, it would have been prima facie obvious to coat the drug eluting segment because this results in nearly zero-order drug release, which would in turn provide constant plasma drug concentrations during the drug release period.
Claims 82 and 90 require various pharmacodynamic properties of the formulation for risperidone delivery, in the alternative. The examiner considers optimizing risperidone release to have been a matter of routine testing for one of ordinary skill in view of the teachings provided by Bellinger on how to achieve steady state extended release of any drug, including risperidone, and for this reason the examiner does not consider the functional language of claims 82 and 90 to patentably define over the cited prior art.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 10, 31, 33-35, 37, 38, 40, 41, 46-48, 51, 52, 55, 57, 82, and 90 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1, 6, 26, 27, 36, 60, 61, 82, 86, 87, 89, 155-160, 162, 163, and 169 of copending Application No. 17774128;
claims 1-7, 9, 10, 11, 13-17, 20-26, 28-30, 40-42, and 54 of copending Application No. 18289326; and
claims 1-25 of copending Application No. 18825519
in view of Bellinger (US 2019/0254966; publication date: 08/22/2019) and Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019).
Inter alia the claims of the copending applications embrace a stellate gastric residence system wherein 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 drug-eluting component. The arms contain segments within them. The system contains a release rate-modulating film coating over at least one drug-eluting component (i.e. segment).
The claims of the copending applications do not require the gastric residence system to contain risperidone.
Bellinger discloses a nearly identical stellate gastroretentive system for extended drug delivery to the stomach and indicates that the drug may be risperidone or the system can be formulated to deliver a multitude of active agents other than risperidone (0196).
The claims of the copending application are considered an obvious variant of the instant claims because, in view of the prior art, the inventive elements relate to the gastroretentive structure itself rather than the particular agent being delivered.
The copending applications do not require a filament circumferentially connecting each arm.
Fitzpatrick, in the analogous art of gastroretentive dosage forms (page 1), discloses some physical linkages that may connect elements of a gastroretentive device, such as fibrous materials including suture material or threads (page 8).
It would have been prima facie obvious to connect the arms of the stellate gastroretentive dosage form embraced by the copending applications using a thread or string (which the examiner considers to fall within the scope of the term “filament” recited in the instant claims) in place of the of the webbing because one of ordinary skill would have recognized it to serve the same purpose of holding the structure in the desired conformation. See MPEP 2143(I)(B).
The claims of the copending applications do not describe the number and location of segments within the arms/elongate members of the stellate system having the arrangement of instant claims 1, 2, 10, and 31.
Bellinger ‘966, describing a very similar gastrorententive dosage form (see: title, abstract, figures), teaches that use of multiple linker sections permits the gastric residence system to break into relatively small pieces after desired residence time for easier passage through the gastrointestinal tract (0090). Bellinger ‘966 teaches further advantages of multi-segment stellate gastroretentive systems including protection against undesired passage of the system into the small intestine, and easy removal if such is required prior to the designed residence time by consumption of an alkaline solution (0087). Bellinger also teaches that curved ends allow the system to fit more snugly into the capsule prior to administration (0097). Finally, Bellinger ‘966 teaches that the ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the system (abstract).
In view of the teachings set forth above, one having ordinary skill in the art would have understood that stellate gastroretentive systems can be designed to deliver risperidone with arms sufficiently long that the system does not pass out of the stomach, wherein the arms are comprised of multiple segments, some of which are degradable such that the arms break apart over time into pieces small enough to pass out of the stomach, where they are subsequently excreted, and that an additional curved cap segment would allow for longer arms, while permitting the folded system to fit snugly within a smaller capsule for easy swallowing.
Claims 1, 2, 10, and 31 as well as claims 33, 35, and 37 are considered prima facie obvious, although the specific arrangement is not recited in the copending applications, because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. Absent evidence of unexpectedly superior performance for the claimed arrangement of prior art segments within the arm, the examiner considers this to have been combining prior art elements according to known methods to yield predictable results (see MPEP 2143(I)(A)).
With regard to claim 40, as noted above, Bellinger discloses that the linkers can be time-dependent (0110).
With regard to claim 41, Bellinger discloses forming segments from HPMCAS (0157 or PCL (0122) in a variety of rations (0184) and it would have been prima facie obvious to one of ordinary skill to optimize dissolution of the segments based on quantity of each polymer. See MPEP 2144.05.
With regard to claim 46, as noted above the segments may be formed from PCL. Bellinger also discloses that the segments may contain radiopaque substances such as bismuth subcarbonate (i.e. (BiO2)CO3; 0209).
With regard to claim 47, as noted above Bellinger teaches enteric linkers (i.e. enteric disintegrating matrix).
With regard to claim 48, as noted above, Bellinger teaches combining PCL with HPMCAS to form an enteric linker having optimized stability in the different regions of the gastrointestinal tract. Bellinger also teaches including poloxamers (i.e. PEG-PPG-PEG block copolymers) in the enteric linkers (e.g. claim 9).
With regard to claim 51, as discussed supra, Bellinger teaches that the carrier polymer-drug (i.e. drug-eluting) comprises PCL and can be formulated to deliver risperidone. This segment can also contain colloidal silicon dioxide (0170).
With regard to claim 52, as discussed in detail above, any segment of the stellate arms disclosed by Bellinger may be formed from PCL.
With regard to claim 55, as discussed in the rejection of claim 57 above, it would have been prima facie obvious to coat the drug eluting segment because this results in nearly zero-order drug release, which would in turn provide constant plasma drug concentrations during the drug release period.
Claims 82 and 90 require various pharmacodynamic properties of the formulation for risperidone delivery, in the alternative. The examiner considers optimizing risperidone release to have been a matter of routine testing for one of ordinary skill in view of the teachings provided by Bellinger on how to achieve steady state extended release of any drug, including risperidone, and for this reason the examiner does not consider the functional language of claims 82 and 90 to patentably define over the cited prior art.
This is a provisional nonstatutory double patenting rejection.
Claims 57, 82, and 90 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 25, 40, 60, 127-129, 131, 132, 135, 136, 143-147, 218, and 224 of copending Application No. 17774132 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims.
Inter alia, the claims of the copending application embrace a gastric residence system, comprising an elastomer core; a plurality of arms (i.e. a number of arms that overlaps with the number required by the instant claims) connected to the core at a proximal end through a plurality of linker components, one linker component of the plurality of the plurality of linker components corresponding to each arm of the plurality of arms, and the plurality of arms extending radially from the proximal end; and a filament circumferentially connecting each arm of the plurality of arms, wherein one or more first arms comprises a carrier polymer and an agent, the one or more first arms attached to a second arm through a polymeric linker, the arm comprising a carrier polymer-agent further comprises a release rate-modulating film coated on the arm; wherein the agent is risperidone.
Claims 82 and 90 require various pharmacodynamic properties of the formulation for risperidone delivery, in the alternative. The examiner considers optimizing risperidone release to have been a matter of routine testing for one of ordinary skill in view of the parameters on how to achieve steady state extended release of any drug, including risperidone, and for this reason the examiner does not consider the functional language of claims 82 and 90 to patentably define over the cited prior art.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 10, 31, 33-35, 37, 38, 40, 41, 46-48, 51, 52, and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 25, 40, 60, 127-129, 131, 132, 135, 136, 143-147, 218, and 224 of copending Application No. 17774,132 (reference application) as applied to claims 57, 82, and 90 above, and further in view of Bellinger (US 2019/0254966; publication date: 08/22/2019).
The relevant limitations of the copending application are set forth above.
The application does not recite a limitation regarding the number and location of segments within the arms/elongate members of the stellate system having the arrangement of instant claims 1, 2, 10, and 31.
Bellinger ‘966, describing a very similar gastrorententive dosage form (see: title, abstract, figures), teaches that use of multiple linker sections permits the gastric residence system to break into relatively small pieces after desired residence time for easier passage through the gastrointestinal tract (0090). Bellinger ‘966 teaches further advantages of multi-segment stellate gastroretentive systems including protection against undesired passage of the system into the small intestine, and easy removal if such is required prior to the designed residence time by consumption of an alkaline solution (0087). Bellinger also teaches that curved ends allow the system to fit more snugly into the capsule prior to administration (0097). Finally, Bellinger ‘966 teaches that the ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the system (abstract).
In view of the teachings set forth above, one having ordinary skill in the art would have understood that stellate gastroretentive systems can be designed to deliver risperidone with arms sufficiently long that the system does not pass out of the stomach, wherein the arms are comprised of multiple segments, some of which are degradable such that the arms break apart over time into pieces small enough to pass out of the stomach, where they are subsequently excreted, and that an additional curved cap segment would allow for longer arms, while permitting the folded system to fit snugly within a smaller capsule for easy swallowing.
Claims 1, 2, 10, and 31 as well as claims 33, 35, and 37 are considered prima facie obvious, although the specific arrangement is not recited in the copending application, because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. Absent evidence of unexpectedly superior performance for the claimed arrangement of prior art segments within the arm, the examiner considers this to have been combining prior art elements according to known methods to yield predictable results (see MPEP 2143(I)(A)).
With regard to claim 40, Bellinger discloses that the linkers can be time-dependent (0110).
With regard to claim 41, Bellinger discloses forming segments from HPMCAS (0157) or PCL (0122) in a variety of rations (0184) and it would have been prima facie obvious to one of ordinary skill to optimize dissolution of the segments based on quantity of each polymer. See MPEP 2144.05.
With regard to claim 46, as noted above the segments may be formed from PCL. Bellinger also discloses that the segments may contain radiopaque substances such as bismuth subcarbonate (i.e. (BiO2)CO3; 0209).
With regard to claim 47, as noted above Bellinger teaches enteric linkers (i.e. enteric disintegrating matrix).
With regard to claim 48, as noted above, Bellinger teaches combining PCL with HPMCAS to form an enteric linker having optimized stability in the different regions of the gastrointestinal tract. Bellinger also teaches including poloxamers (i.e. PEG-PPG-PEG block copolymers) in the enteric linkers (e.g. claim 9).
With regard to claim 51, as discussed supra, Bellinger teaches that the carrier polymer-drug (i.e. drug-eluting) comprises PCL and can be formulated to deliver risperidone. This segment can also contain colloidal silicon dioxide (0170).
With regard to claim 52, as discussed in detail above, any segment of the stellate arms disclosed by Bellinger may be formed from PCL.
With regard to claim 55, as discussed in the rejection of claim 57 above, it would have been prima facie obvious to coat the drug eluting segment because this results in nearly zero-order drug release, which would in turn provide constant plasma drug concentrations during the drug release period.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 57, 82, and 90 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 1433, 34, 41, 52, 57, 65, 68, 72, 75, 87, 116, 137-139, 142, and 145 of copending Application No. 17774127 (reference application) in view of Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019).
Inter alia, the claims of the copending application embrace a gastric residence system comprising: one or more arms comprising: a carrier polymer, at least one agent or a pharmaceutically acceptable salt thereof, and a release rate-modulating film coated on at least a portion of the surface of the arm; and a central elastic polymeric component; wherein the one or more arms are each connected to the central elastic polymeric component via a separate linker component; wherein the gastric residence system is configured to be folded and physically constrained during administration and is configured to assume an open retention shape upon removal of a constraint; wherein change between the folded shape and the open retention shape is mediated by the elastic polymeric component that undergoes elastic deformation when the residence system is in the folded shape and recoils when the gastric residence system assumes the open retention shape; and wherein said linker degrades, dissolves, disassociates, or mechanically weakens in a gastric environment which results in loss of retention shape integrity and passage out of a gastric cavity. The system may be used to deliver risperidone as the agent.
The copending application does not require a filament circumferentially connecting each arm.
Fitzpatrick, in the analogous art of gastroretentive dosage forms (page 1), discloses some physical linkages that may connect elements of a gastroretentive device, such as fibrous materials including suture material or threads (page 8).
It would have been prima facie obvious to connect the arms of the stellate gastroretentive dosage form embraced by the copending application using a thread or string (which the examiner considers to fall within the scope of the term “filament” recited in the instant claims) in place of the of the webbing because one of ordinary skill would have recognized it to serve the same purpose of holding the structure in the desired conformation. See MPEP 2143(I)(B).
Claims 82 and 90 require various pharmacodynamic properties of the formulation for risperidone delivery, in the alternative. The examiner considers optimizing risperidone release to have been a matter of routine testing for one of ordinary skill in view of the parameters on how to achieve steady state extended release of any drug, including risperidone, and for this reason the examiner does not consider the functional language of claims 82 and 90 to patentably define over the cited prior art.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 10, 31, 33-35, 37, 38, 40, 41, 46-48, 51, 52, and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 14,33, 34, 41, 52, 57, 65, 68, 72, 75, 87, 116, 137-139, 142, and 145 of copending Application No. 17774127 (reference application) in view of Fitzpatrick et al. (WO 2019016560; publication date: 01/24/2019) as applied to claims 57, 82, and 90 above, and further in view of Bellinger (US 2019/0254966; publication date: 08/22/2019).
The relevant limitations of the copending application and disclosure of Fitzpatrick are set forth above.
The application does not recite a limitation regarding the number and location of segments within the arms/elongate members of the stellate system having the arrangement of instant claims 1, 2, 10, and 31.
Bellinger ‘966, describing a very similar gastrorententive dosage form (see: title, abstract, figures), teaches that use of multiple linker sections permits the gastric residence system to break into relatively small pieces after desired residence time for easier passage through the gastrointestinal tract (0090). Bellinger ‘966 teaches further advantages of multi-segment stellate gastroretentive systems including protection against undesired passage of the system into the small intestine, and easy removal if such is required prior to the designed residence time by consumption of an alkaline solution (0087). Bellinger also teaches that curved ends allow the system to fit more snugly into the capsule prior to administration (0097). Finally, Bellinger ‘966 teaches that the ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the system (abstract).
In view of the teachings set forth above, one having ordinary skill in the art would have understood that stellate gastroretentive systems can be designed to deliver risperidone with arms sufficiently long that the system does not pass out of the stomach, wherein the arms are comprised of multiple segments, some of which are degradable such that the arms break apart over time into pieces small enough to pass out of the stomach, where they are subsequently excreted, and that an additional curved cap segment would allow for longer arms, while permitting the folded system to fit snugly within a smaller capsule for easy swallowing.
Claims 1, 2, 10, and 31 as well as claims 33, 35, and 37 are considered prima facie obvious, although the specific arrangement is not recited in the copending application, because one having ordinary skill would have predicted the above benefits from the claimed arrangement of segments. Absent evidence of unexpectedly superior performance for the claimed arrangement of prior art segments within the arm, the examiner considers this to have been combining prior art elements according to known methods to yield predictable results (see MPEP 2143(I)(A)).
With regard to claim 40, Bellinger discloses that the linkers can be time-dependent (0110).
With regard to claim 41, Bellinger discloses forming segments from HPMCAS (0157) or PCL (0122) in a variety of rations (0184) and it would have been prima facie obvious to one of ordinary skill to optimize dissolution of the segments based on quantity of each polymer. See MPEP 2144.05.
With regard to claim 46, as noted above the segments may be formed from PCL. Bellinger also discloses that the segments may contain radiopaque substances such as bismuth subcarbonate (i.e. (BiO2)CO3; 0209).
With regard to claim 47, as noted above Bellinger teaches enteric linkers (i.e. enteric disintegrating matrix).
With regard to claim 48, as noted above, Bellinger teaches combining PCL with HPMCAS to form an enteric linker having optimized stability in the different regions of the gastrointestinal tract. Bellinger also teaches including poloxamers (i.e. PEG-PPG-PEG block copolymers) in the enteric linkers (e.g. claim 9).
With regard to claim 51, as discussed supra, Bellinger teaches that the carrier polymer-drug (i.e. drug-eluting) comprises PCL and can be formulated to deliver risperidone. This segment can also contain colloidal silicon dioxide (0170).
With regard to claim 52, as discussed in detail above, any segment of the stellate arms disclosed by Bellinger may be formed from PCL.
With regard to claim 55, as discussed in the rejection of claim 57 above, it would have been prima facie obvious to coat the drug eluting segment because this results in nearly zero-order drug release, which would in turn provide constant plasma drug concentrations during the drug release period.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617
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