DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/19/2026 has been entered.
Election/Restrictions
Claims 17-19, 21, 25, 27 and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group and/or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 4/5/2024.
Response to Arguments
All of Applicant’s arguments filed 2/19/2026 have been fully considered.
Obviousness Rejections
Difference over Varum
Applicant argues that Varum does not teach the particular formulation claimed and the working examples only use buffer in amounts of 1% and the examples teach away from the current invention.
This is not persuasive as the teachings of a reference are not limited to the working embodiments and the use of non-exemplified or non-preferred embodiments do not constitute a teaching away as the reference does not criticize or discredit the use of other amounts of buffer agent and in fact teaches amounts of 0.1-50% to be suitable for use.
Data Supporting the Non-Obviousness of the Present Invention
In summary on pages 12-15, Applicant argues that the data in the specification, in particular Ex. 1 and Comparative Ex. 3, provide evidence of a significant and unexpected effect.
This is not persuasive. Applicant remarks that the data presented represents a technically significant and surprising result, particularly in the context of reducing or eliminating the “food effect,”, this is not persuasive as Applicant has not established what would have been expected by a skilled artisan when altering the amounts of buffer agent present. Varum teaches that the buffer agent directly affects the dissolution rate of the outer polymer layer, as such changing the amounts of buffer agent used is expected to result in faster or slower dissolution of the outer layer polymer which in turn effects the amount of active delivered and when the active is delivered. Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. See MPEP 716.02. Applicant has no established that these differences are unexpected.
Applicant has not provided any evidence that the differences in Fig. 4 and 3 were statistically significant. Applicant has not provided any error bars or other explanation of the data in the spec suggesting that the results represent a single experiment. See McNeil-PPC, Inc. V. L. Perrigo Co., 337 F.3d 1362, 1370 (Fed. Cir. 2003) (Finding evidence unpersuasive that "was based on the results of a study involving only nine participants and thus did not rise to the level of statistical significance" and finding the studies were "not shown to be reproducible."). Therefore "even assuming that the test methodology were valid, the test results were not statistically significant. These are all determinations of credibility, reliability, and weight." Novartis Pharm. Corp. V. Watson Labs., Inc., 611 Fed. Appx. 988, 999 (Fed. Cir. 2015). As taught by Varum [0131] the time between initial exposure to condition suitable for drug release and the start of drug release (i.e. lag time) is dependent on a number of factors including coating thickness, composition and can vary from one patient to the next which suggest that the data obtained in Fig. 3 and 4 is not necessarily reproducible across different patients. The Examiner would also like to note that the data presented only tests 30% buffer, but the claims are directed to 30-60%.
Claimed Invention is Not Obvious
Applicant argues that Varum does not discuss “food effect” and does not teach the advantageous technical effects of the instant invention.
This is not persuasive, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Applicant argues that a skilled person looking to build upon the teaching of Varum would look first to the exemplified formulations instead of pursuing a non-exemplified alternative. Varum provides no teaching or suggestion that would motivate such an initial departure from its exemplified and preferred embodiments and nothing is Varum provides motivation to select HPMC over any of the other polymers for any reason, let alone with a view of solving the problem of reducing or eliminating the "food effect".
This is not persuasive as the teachings of a reference are not limited to the exemplified embodiments and Varum specifically teaches that HPMC is a suitable non-ionic polymer able to be used in the inner layer, thus the use of this polymer is prima facie obvious yielding no more than expected from such an arrangement. Applicant has provided no data that using HPMC in the inner layer provides an unexpectedly superior effect.
Applicant argues that a skilled artisan would then be required to select a buffer agent amount of 30 to about 60 wt%. While Varum discloses in a general context that a buffer agent may be present in the inner layer in an amount from 0.1 to 50 wt % Varum expressly teaches that where the soluble (or third) polymeric material of the inner layer is a non-ionic polymer, the buffer agent is usually present in an amount from 10 wt% to 30 wt%. There is no teaching, suggestion, or motivation in Varum to select a buffer agent concentration that begins at the upper boundary of that preferred range and extends well beyond it. Selecting a buffer agent amount of 30 wt% to about 60 wt% is therefore contrary to Varum's express teaching.
This is not persuasive. While Applicant teachings above of Varum are correct, the amount of 10 wt% to 30 wt% of buffer when using HPMC is considered a preferred embodiment and Varum still teaches that amounts up to 50% can be used (i.e. non-preferred) and preferred embodiments do not teach away from using non-preferred embodiments as Varum does not criticize or discredit the use of 30-50% of buffer when using HPMC.
Applicant argues that Varum fails to teach polyethylene glycol (PEG) in the inner layer. Varum neither teaches nor suggests including PEG in the inner layer, let alone in a HPMC-based inner layer. In fact, Varum teaches away from such a combination by expressly stating a clear preference for using a single polymeric material alone for the inner layer (see [0110]) and further indicates that the polycarboxylic acid polymer is preferably used in both the inner and outer layers (see [0109]).
This is not persuasive as Varum teaches that mixtures of non-ionic polymers in the inner layer can be used [0110], while a single polymer is listed as preferred for use, this does not teach away from using a mixture as Varum specifically teaches that mixture can be used and preferred embodiments do not teach away from using non-preferred embodiments as Varum does not criticize or discredit the use of mixtures.
Applicant argues that while Bravo Gonzalez discusses “food effect” there is no suggestion in these passages, or anywhere else in Bravo Gonzalez, that the "food effect" could be addressed by modifying the composition of the inner layer, let alone by incorporating PEG into an HPMC-based inner layer with unusually high levels of a phosphate buffer agent.
This is not persuasive, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). As discussed below, a skilled artisan would have been motivated to use a combination of HPMC and PEG as these are taught by Bravo Gonzalez to be equivalent non-ionic polymeric materials for use in an inner layer comprising buffering agents and a base. One of skill in the art would have a reasonable expectation of success as both Varum and Bravo Gonzalez teach delayed released formulations of 5ASA in a core, wherein the cores comprises the same or similar inner coatings, outer coatings and isolation layers and Varum teaches that mixture of polymers can be used [0110].
Applicant argues that Bravo Gonzalez merely discloses a list of potential non-ionic polymers that may be used in its inner layer, including HPMC, PVA, and PEG, among others (see [0084]). Bravo Gonzalez does not suggest any particular combination of polymers, let alone the specific combination of HPMC and PEG. Outside of the benefit of highsight Office Action has not provided any reason why the skilled person, starting from Varum, would have been motivated to specifically select PEG from the numerous disclosed and equally weighted alternatives in Bravo Gonzalez.
This is not persuasive as Bravo Gonzalez teaches 7 non-ionic polymers to be suitable for use, thus the selection of HPMC and PEG from a finite list is prima facie obvious absent evidence of criticality.
Applicant argues that Bravo Gonzaez teaches amounts of Buffer of 0.1-20% which is lower than the claimed amounts, thus a skilled artisan would be directed to lower buffer concentrations and not toward the higher concentration claimed.
This is not persuasive as the rejection present in not based on attempting to incorporate the composition of Bravo Gonzalez into the composition of Varum. Bravo Gonzalez is cited only for the proposition that HPMC and PEG are equivalent inner layer non-ionic polymers.
Double Patenting Rejection
Applicant’s arguments regarding the double patenting rejections are not persuasive as the double patenting rejections have been modified below to address the claims as newly amended.
Modified/Maintained 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
Claim(s) 1, 5-6, 8, 11, 14, 35 and 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Varum (US 2016/0250232) and Bravo Gonzalez (US 2015/0132380).
Regarding claim 1: Varum discloses a delayed release drug formulation for oral administration for use in accelerating drug release in the colon of said subject. The formulation comprises a core comprising a drug, an isolation layer coating the core and an outer layer coating the isolation layer, wherein the outer layer comprises an outer layer and an inner layer, reading on inner layer, outer layer and isolation layer as recited by instant claim 1. The outer layer comprises a pH dependent soluble polymeric material with a pH threshold at about pH 5 or above (Varum – claim 50 and 65). Varum teaches the pH threshold to preferably be about 6.5 or above [0070]. Varum teaches the tablet cores comprising be 5ASA and teaches 5ASA to be used in amounts of 400mg, 800mg and 1200mg and teaches the formation of tablet core.(working examples 1-5 and Figures and Varum – claim 81).
Varum teaches the outer layer to be a mixture of pH dependently soluble 2nd polymeric material in admixture with the digestible 1st polymeric materials which are susceptible to attack by colonic bacteria (i.e. starch) [0087 and 0057]. Varum teaches that for colonic release formulations, the pH dependently 2nd polymeric material is preferably Eudragit S 30:70 (reading on the claimed film-forming enteric poly(methacrylic acid/methyl methacrylate) co-polymer having an acid:ester ratio of about 1:2 of the outer layer, as evidenced by page 9, lines 5-10 of the originally filed specification) [0086 and 0091]. Varum teaches the 1st polymeric material to preferably be starch (elected species) [0056].
Regarding the claimed “enzymatically degradable starch”, Varum teaches the starch used to be a material susceptible to attack by colonic bacteria and this can be determined by common general knowledge of a skilled artisan. For example, a pre-determined amount of a given material could be exposed to an assay containing an enzyme from a bacterium found in the colon and the change in weight of the material over time may be measured [0057]. The instant specification teaches the enzymatically degradable polymer to be degraded by one or more bacterial enzymes found in the colon of the subject (i.e. colonic bacterial enzymes) and teaches that a skilled artisan is capable of determining which materials are suitable by taking a pre-determined amount of a given material could be exposed to an assay containing an enzyme from a bacterium found in the colon and the change in weight of the material over time may be measured. As such the 1st polymer starch of Varum is deemed to read on enzymatically degradable starch.
Varum teaches an inner layer, which is positioned between to the isolation layer and the outer layer. A suitable polymer for use (i.e. third polymeric material) includes HPMC (elected species) and when HPMC is used the inner layer preferably comprises a base and a buffer agent ([0108-0109] and Varum – claims 50 and 91). The buffer is taught to be used in amounts ranging from about 0.1-50%, usually about 10-30% based on the dry weight of the third polymeric material (i.e. HPMC) which overlaps with the claimed 30 to about 60wt% [0119] and overlapping ranges are prima facie obvious absent evidence of criticality.
Regarding claims 1, 6, 8, 11 and 35: Varum teaches the inner layer to preferably comprise a base and a preferred base for use is sodium hydroxide and a preferred buffer is potassium dihydrogen phosphate (i.e. phosphate buffer salt) [0112 and 0118]. The buffer is taught to be used in amounts ranging about 0.1-50%, usually 10-30% based on the dry weight of the 3rd polymeric material (i.e. HPMC, inner layer) [0119] which overlaps with the claimed 30-60% and the claimed 30-50%, 30-40% and 30-50% and overlapping ranges are prima facie obvious absent evidence of criticality.
Regarding claim 1: Varum teaches the isolation layer to preferably comprise HPMC [0030].
Regarding claims 1 and 5: Varum teaches that the inner layer typically has a polymer coating amount from 2-10 mg/cm2 based on the dry weight of the 3rd polymeric material, i.e. the polymeric material of the inner layer and HPMC [0038 and 0121].
Regarding claim 1 and 14: Varum teaches that the coating amount of the polymeric materials in the outer coating ranges from 2-10 mg/cm2 based on the dry weight of the total polymeric material. While this is not taught to be “by dry weight of the enteric poly(methacrylic acid/methyl methacrylate) co-polymer”, as discussed above, the 1st and 2nd polymeric materials are present in a mixture of at least 10:90 which provides a range of enteric polymer present in the outer layer that overlaps with the claimed ranges. For example if the enteric polymer makes up 90% of the outer layer, then the weight of enteric polymer falls between 1.8-9 mg/cm2.
Regarding claim 39: Varum teaches a suitable inner polymer (i.e. third polymeric material), to be HPMC selected from a finite number of options (Varum - 91). Varum also teaches that mixtures of film-forming polymers may be used as appropriate, which implies that mixtures need not be used, thus the use of HPMC as the sole inner layer polymer is prima facie obvious.
Varum does not teach a specific embodiment having all the claimed elements.
That being said, however, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. AG. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is... a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to have selected various combinations of various disclosed components such as outer layer, inner layer and isolation layer, 5ASA, etc. to formulate a drug release tablet from within a prior art disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
However, Varum does not teach the inner layer (i.e. 3rd polymeric material) to comprise a mixture of HPMC and polyethylene glycol.
Bravo Gonzalez teaches the delayed release of a drug to the colon using a formulation comprising a core and a coating for the core. The core comprises a drug and the coating comprises an outer layer and at least one layer between the core and the outer layer selected from the group consisting of an isolation layer and an inner layer. The outer layer comprises a mixture of a first polymeric material which is susceptible to attack by colonic bacteria, and a second polymeric material which has a pH threshold at about pH 5 or above. The inner layer comprises a 3rd polymeric material, at least one buffering agent and a base (Abs). A suitable drug for release is 5ASA [0115]. Polymeric materials for the outer layer include starch and Eudragit S [0182]. The isolation later can comprises HPMC [0099].
Bravo Gonzalez teaches that the third polymer material (i.e. the inner layer) can be non-ionic polymers which include HPMC and polyethylene glycol (PEG), selected from a finite number of non-ionic polymers and mixtures are taught to be suitable used [0084-0085].
It would have been prima facie obvious to modify the teachings of Varum with those of Bravo Gonzalez. A skilled artisan would have been motivated to use a combination of HPMC and PEG as these are taught by Bravo Gonzalez to be equivalent non-ionic polymeric materials for use in an inner layer comprising buffering agents and a base. One of skill in the art would have a reasonable expectation of success as both Varum and Bravo Gonzalez teaches formulation delayed released formulations of 5ASA in a core, wherein the cores comprises the same or similar inner coatings, outer coatings and isolation layers and Varum teaches that mixture of polymers can be used [0110].
New 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 1, 5-6, 8, 11, 14, 16, 35 and 39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11,517,534 in view of Varum (US 2016/0250232) and Bravo Gonzalez (US 2015/0132380).
US’534 discloses delayed release drug formulation for oral administration comprising a core and a coating for the core, the core comprising a drug and the coating comprising an outer layer and an inner layer. The outer layer, for providing intestinal release, comprising a mixture of a polymeric material which is susceptible to attack by colonic bacteria and a second (film-forming) polymeric material (reading on enteric polymer) which has a pH threshold at about pH 5 or above. These are taught to be used in a ratio of up to about 60:40. The inner layer is taught to comprise non-ionic polymer such as HPMC (mixtures are not required) and at least one additive selected from a buffer agent and a base, such as potassium dihydrogen phosphate and sodium hydroxide. US’534 teaches the buffer agent to be present in amounts ranging from 10 to about 30 wt.% based on the dry weight of the third polymeric material, this amount overlaps with the claimed ranges of buffer. US’534 teaches the outer layer has a thickness from about 2 mg/cm2 to about 10 mg/cm2 based on the total polymeric material. US’534 teaches the drug to be 5ASA.
However, US’534 does not teach the polymeric material which is susceptible to attack by colonic bacteria to be an enzymatically degradable polymer that is degraded by colonic bacteria, does not teach the poly(methacrylic acid/methyl methacrylate) co-polymer as claimed and does not the amounts of non-ionic polymer and enteric polymer used as recited by instant claim 5 and 14, and does not teach the active to be 5ASA in amounts of 400-1600mg.
The teachings of Varum are discussed above and are incorporated into this rejection.
Based on the teachings of Varum a skilled artisan would have been motivated to use starch as the polymeric material which is susceptible to attack by colonic bacteria along with Eudragit S as this is shown to be effectively used in outer coating comprising polymers having a pH threshold at about pH 5+ such as those desired by US’534. One of skill in the art would have also been motivated to use the HPMC in the inner layer and the enteric polymer in the amounts taught by Varum as its prima facie obvious to pursue the known options within the technical grasp of the skilled artisan to achieve predictable results of formulating delayed release formulations for oral administration. US’534 teaches the outer layer has a thickness from about 2 mg/cm2 to about 10 mg/cm2 based on the total polymeric material. While this is not taught to be by dry weight of the enteric polymer, as discussed above the 1st and 2nd polymeric materials are present in a mixture of up to 60:40 which provides a range of enteric polymer present in the outer layer that overlaps with the claimed ranges. One of skill in the art would have also been motivated to use 5ASA in the amounts taught by Varum to be suitable for use as the active agent in the core as Varum teaches this agent to be suitable used in these types of formulations.
However, US’534 does not teach the inner layer to also comprise PEG.
The teachings of Bravo Gonzalez are discussed above and are incorporated into this rejection and the claims are obvious for the same reasons.
Claims 1, 5-6, 8, 11, 14, 16 and 35 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. 11,534,406 in view of Varum (US 2016/0250232) and Bravo Gonzalez (US 2015/0132380).
US’406 discloses delayed release drug formulation for oral administration to deliver a drug the intestine of a subject comprising a core and a coating for the core, the core comprising a drug and the coating comprising an outer layer and at least one layer between the core (i.e. inner layer). The outer layer comprising a mixture of a first polymeric material which is susceptible to attack by colonic bacteria and a second polymeric material such as polymethacrylate polymers (enteric film-forming polymer) which has a pH threshold at about pH 5 or above. These are taught to be used in a ratio of up to about 60:40. The inner layer is taught to comprise non-ionic polymer such as HPMC (mixtures are not required), and at least one additive selected from a buffer agent and a base, such as potassium dihydrogen phosphate and sodium hydroxide. US’406 teaches the buffer agent to be present in amounts ranging from 10 to about 30wt% based on the dry weight of the third polymeric material, this amount overlaps with the claimed ranges. US’406 teaches the non-ionic polymer being present in the inner layer an amount from about 2 mg/cm2 to about 10 mg/cm2 based on the dry weight of the polymer. US’406 teaches the polymeric materials are present in amounts of about 2 mg/cm2 to about 10 mg/cm2 based on the total dry weight of the polymeric material. The formulation is further taught to comprise an isolation layer comprising HPMC. US’406 teaches the drug to be 5ASA.
However, US’406 does not teach the polymeric material which is susceptible to attack by colonic bacteria to be an enzymatically degradable polymer that is degraded by colonic bacteria, does not teach the poly(methacrylic acid/methyl methacrylate) co-polymer as claimed and does not teach the active to be 5ASA in the claimed amounts.
The teachings of Varum are discussed above and are incorporated into this rejection.
Based on the teachings of Varum a skilled artisan would have been motivated to use starch as the polymeric material which is susceptible to attack by colonic bacteria along with Eudragit S as this is shown to be effectively used in outer coating comprising polymers having a pH threshold at about pH 5+ such as those desired by US’406. One of skill in the art would have also been motivated to use 5ASA in the amounts taught by Varum as the active agent in the core as Varum teaches this agent to be suitable used in these types of formulations.
However, US’506 does not teach the inner layer to also comprise PEG.
The teachings of Bravo Gonzalez are discussed above and are incorporated into this rejection and the claims are obvious for the same reasons.
Claims 1, 5-6, 8, 11, 14, 16, 35 and 39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of US Patent 12,370,146 (previously copending Application No. 17/309554) in view of Varum (US 2016/0250232) and Bravo Gonzalez (US 2015/0132380). US’146 discloses delayed release drug formulation for oral administration to deliver a drug to the colon. The formulation comprises a core comprising a drug; an outer coating comprising a mixture of an enzymatically degradable polysaccharide which is degradable by colonic bacterial enzymes, a film-forming enteric polymer having a pH threshold at about pH 6 or above, wherein the proportion of the enzymatically degradable polysaccharide to the film- forming enteric polymer in the outer coating preparation is in a range from 10:90 to 50:50. The formulation further comprises an inner layer comprising a film-forming non-ionic polymer that is soluble in gastrointestinal fluid, a buffer agent and a base. The formulation also comprises an isolation layer located on the surface of the core, said isolation layer comprising a film-forming non-ionic polymer that is soluble in gastrointestinal fluid.
However, US’146 does not claimed amounts of buffer and does not teach the limitations of claims 5, 8, 11, 14 and 16 and does not teach the active to be 5ASA.
The teachings of Varum are discussed above and are incorporated into this rejection.
Based on the teachings of Varum a skilled artisan would have been motivated to use the HPMC in the inner layer (in the taught amounts), use HPMC as the isolation polymer as taught by Varum and use Eudragit S in the outer layer as its prima facie obvious to pursue the known options within the technical grasp of the skilled artisan to achieve predictable results of formulating delayed release formulations for oral administration. US’146 teaches the outer layer has a thickness from about 2 mg/cm2 to about 10 mg/cm2 based on the total polymeric material. While this is not taught to be by dry weight of the enteric polymer, as discussed above the 1st and 2nd polymeric materials are present in a range of 10:90 to 50:50 which provides a range of enteric polymer present in the outer layer that overlaps with the claimed ranges. One of skilled in the art would have also been motived to use sodium hydroxide and about 10-30% of potassium dihydrogen phosphate as Varum teaches these to be suitable buffer/base agents for use in composition similar to those of US’146 and teaches that the buffer agent increases the buffer capacity in the dissolving inner layer and assists the ionization and dissolution of the polymer(s) in the outer layer. It is believed that, for a given pH, the higher the buffer capacity, the faster the rate of polymer dissolution. In embodiments where there is a base in the inner layer, the buffer agent helps maintains the alkaline environment under the outer layer once intestinal fluid penetrates the outer layer [0116]. One of skill in the art would have also been motivated to us 5ASA in the amounts taught by Varum as the active agent in the core as Varum teaches this agent to be suitable used in these types of formulations. One of skill in the art would have also been motivated to use the HPMC in the inner layer in the amounts taught by Varum as its prima facie obvious to pursue the known options within the technical grasp of the skilled artisan to achieve predictable results of formulating delayed release formulations for oral administration.
However, US’146 does not teach the inner layer to also comprise PEG.
The teachings of Bravo Gonzalez are discussed above and are incorporated into this rejection and the claims are obvious for the same reasons.
Conclusion
No claims are allowable.
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/JENNIFER A BERRIOS/Primary Examiner, Art Unit 1613
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