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 1-12 are pending, presented for examination, and rejected as set forth in greater detail below.
Claim Interpretation
Applicants claims are directed to methods of preparing active-agent containing microgranules by providing a neutral support core and then spraying onto that neutral support an aqueous suspension containing a particular polymer, which by applicants election is represented by the commercially available polymer known as EUDRAGIT L30D. Step b’ of the process claimed then requires an active be “dusted” onto the suspension coated core, which dependent claims specify is addressed by, among others, 5-aminosalicylic acid. Art describing the application of a solid or micronized solid form of an active agent such as 5-aminosalicylic acid will be considered sufficient to address the “dusting” of claim 1-b’. Element c’ of the claim requires the combination of steps a’ and b’ be repeated until a desired content of active agent is obtained. Step d requires that the microgranules so obtained them be provided with an enteric coating combining, per applicants election, three polymers corresponding to the commercially available enteric polymers EUDRAGIT L100, EUDRAGIT S100, and EUDRAGIT RL100 in particular ratios.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Makino (U.S. 5,026,560), in view of Bhasale (WO2011/036677), and JP 2009523833 (“JP’833”)(machine translation provided).
Makino describes the production of granules containing seed core which is coated by an aqueous solution containing a binder, which is coated by a powder containing a drug to provide spheres of narrow size distribution. (Co.1, L.32-37; 59-63). Makino indicates that the powdered drugs to be so formulated are not particularly limited, but include drugs for the digestive system including the presently claimed 5-aminosalicylic acid. (Col.2, L.4-20; Col.3, L.45-61)). The seed cores are described as including the neutral NONPAREIL sucrose/corn starch or crystalline cellulose having a size of mesh 14-80. (Col.3, L.30-35). Makino indicates that the binders can be provided as aqueous compositions, but fail to indicate that the aqueous composition can include at least one anionic (meth)acrylate copolymer that is soluble at a pH greater than 5.5. (Col.3, L.36-40). However, Bhasale indicates that the EUDRAGIT L30D copolymer applicants employ in the aqueous coating solution was, at the time the present application was filed, known to be used in the pharmaceutical granule coating arts as a binder polymer suitable for drug formulations targeting the GI tract. (Pg.5, L.23 – Pg.6, L.8). While Makino does not recite the sequence or repetition of the liquid and powder coating steps as is recited by the present claims, applicants are reminded that simply rearranging or duplicating elements has no patentable significance unless a new and unexpected result is produced. In re Harza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960). Makino indicates that these coated cores may then be subjected to additional coating, including enteric coating such as by any of the EUDRAGIT polymers. (Col.4, L.15-27). Makino describes using a CF granulator at various rotor speeds to coat nonpareil cores with binder solutions and drug powders, which the skilled artisan would recognize is a form of conventional turbine used to apply powder coats mechanically. (Col.5-7, Examples 2-10).
Despite suggesting a process by which nonpareil cores are coated by an aqueous fluid containing a binder such as EUDRAGIT L30D to which is then applied a powder composition containing an active agent such as 5-aminosalicylic acid to provide drug-containing microgranules which are then to be enteric coated by the application of a EUDRAGIT polymer composition, neither Makino nor Bhasale suggest the combination of anionic (meth)acrylate copolymer soluble at a pH great than 6, anionic (meth)acrylate copolymer soluble at a pH great than 7, and anionic (meth)acrylate copolymer insoluble in aqueous medium such as the commercially available enteric polymers EUDRAGIT L100, EUDRAGIT S100, and EUDRAGIT RL100, respectively, elected by applicants.
This is cured by the teachings of JP’83, which establishes that each of the presently claimed EUDRAGIT L100, EUDRAGIT S100, and EUDRAGIT RL100 are not only known to be usefully employed as enteric coating polymers, but that advantages in protection active agent release can be obtained by combining multiple such methacrylic acid polymers. (Pg.6-7, 9-10). While the particular ratio of EUDRAGIT L100, EUDRAGIT S100, and EUDRAGIT RL100 recited by the instant claims is not specifically described by the teachings of the JP’833 document, it must be remembered that here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, the art establishes not only that combinations of EUDRAGIT polymers may serve as enteric coating polymers, but that by altering the composition and content of the EUDRAGIT coatings, properties such as gastric resistance and swellability of the polymer coating can be adjusted.
It therefore would have been prima facie obvious to one of ordinary skill in the art at the time the instant application was filed to have combined the EUDRAGIT L100, EUDRAGIT S100, and EUDRAGIT RL100 enteric polymers and used such a combination as an enteric coating in the process by which nonpareil cores are coated by an aqueous fluid containing a binder such as EUDRAGIT L30D to which is then applied a powder composition containing an active agent such as 5-aminosalicylic acid to provide drug-containing microgranules which are then to be enteric coated by the application of a EUDRAGIT polymer composition suggested by the teachings of Makino and Bhasale owing to the utility these EUDRAGIT polymers are known to possess.
Response to Arguments
Applicant's arguments filed 8 December 2025 have been fully considered but they are not persuasive.
Applicants assertion that the presently claimed sequence of spraying a liquid which is then coated with a powder is distinguishable from the process described by Makino is unpersuasive, for it has long been held that the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946). Makino, buy failing to criticize, discourage, or otherwise discredit such an arrangement of process steps, cannot therefore “teach away from” such an arrangement. In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). Here, Makino indicates the spraying of the binder liquid and the spraying of the drug powder onto nonpareil cores provides drug containing cores with excellent hardness, shape, size, and drug content.
Applicants argument that the step of Makino which specifically introduces a EUDRAGIT polymer as a final layer distinct from that of the anionic (meth) acrylate copolymer of step a) misapprehends the reason for the Examiner’s reliance on this teaching of Makino, which is not to address step a), but rather step d) of the present claims.
Applicants argue that nothing of the art specifies that the dosage form is configured to provide for colonic delivery. Applicants are reminded that they acknowledge that it is the anionic (meth)acrylate copolymer EUDRAGIT S100 applied in step d) of the process that provides for the targeted delivery of the active agent to the colon. See Specification pg.6. Applicants are reminded that products of identical chemical composition cannot have mutually exclusive properties. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. As the Examiner has articulated a rationale by which a skilled artisan would apply as the coating in step d) of the claimed process the EUDRAGIT S100 applicants own specification acknowledges provides for the colonic delivery claimed, nothing more is required. The reason or motivation to modify a prior art reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention).
Applicants assertion that the fact that repeating steps of coating the cores with binder fluid and powdered drug compositions provides for a skilled artisan’s ability to modify the amount of drug contained in each core is unpersuasive, because this is precisely what a skilled artisan would expect to see by repeating a step by which a drug containing powder is adhered to a core with a binder fluid. In a like manner, as the production of a core dosage form possessing excellent hardness, shape, size, and drug content is an explicit goal of the Makino process. See Makino Col.1, L.19-63).
Applicants argument that Makino does not teach the claimed arrangement of copolymer combinations is, so far as it goes, not inaccurate: the Examiner has not indicated that, considered in a vacuum, Makino does. Applicants are reminded that it is not possible to establish the non-obviousness of an invention rendered obvious by the combined teachings of multiple prior art references by arguing that each of the references relied upon fails to teach the entirety of the invention which has been claimed; the absence of a single anticipatory reference is implied by both the reliance on the combined teachings of multiple references as well as the fact that the rejection being made is one of obviousness under 35 U.S.C. 103 rather than any of the subsections of 35 U.S.C. 102. MPEP § 2145(IV), see In re Keller, 642 F.2d 413, 426 (C.C.P.A. 1981) (citing Application of Young, 403 F.2d 754, 757 (C.C.P.A. 1968) (indicating that "[O]ne cannot show non-obviousness by attacking references individually where ... the rejections are based on combinations of references"). Here, Makino indicates that neutral cores may be coated by solutions containing binders which adhere powdered drug compositions to form drug-containing granules, which are then coated by enteric EUDRAGIT polymers to provide orally deliverable dosage forms. Bhasale is then relied on to establish that the particular (meth)acrylate copolymer applicants use in the binder solution of step a) was, at the time the instant application was filed, known to be used in the pharmaceutical coating arts as a binder. JP’83 was then relied on to establish that each of the presently claimed EUDRAGIT L100, EUDRAGIT S100, and EUDRAGIT RL100 copolymers applicants acknowledge provide for the targeted colonic release claimed were not only known to individually be usefully employed as enteric coating polymers, but that advantages in protection active agent release can be obtained by combining multiple such methacrylic acid polymers.
Applicants next move their piecemeal analysis of the art to consideration of the Bhasale reference. Applicants assertion that because Bhasale utilizes a different active agent, its teachings cannot suitably be relied on for combining with the Makino reference. Applicants are reminded that in order for a reference to be properly available for use in an obviousness rejection under 35 U.S.C. 103, the reference must be analogous art to the claimed invention. In re Bigio, 381 F.3d 1320, 1325, 72 USPQ2d 1209, 1212 (Fed. Cir. 2004). “Under the correct analysis, any need or problem known in the field of endeavor at the time of the invention and addressed by the patent [or application at issue] can provide a reason for combining the elements in the manner claimed.” KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 420, 82 USPQ2d 1385, 1397 (2007). The scope of analogous art is to be considered broadly. Wyers v. Master Lock Co., No. 2009-1412, 2010 WL 2901839 (Fed. Cir. 2010). Analogous art is not limited to references in the field of endeavor of the invention, but also includes references that would have been recognized by those of ordinary skill in the art as useful for the desired purpose. Agrizap, Inc. v. Woodstream Corp., 520 F.3d 1337 (Fed. Cir. 2008). Here, as each of Makino and Bhasale concern coated cores of pharmaceutical active agents employing binder solutions, their combination is proper.
Applicants next assert a sequence of allegations concerning what Bhasale does not teach. As Bhasale has been relied upon for a single reason, establishing that the EUDRAGIT L30D copolymer applicants employ as the binder in step a) of the process was, at the time of the instant applications filing, known to be useful as a binder per the requirements of Makino. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981), In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000)(indicating that all elements of each prior art reference need not read on the claimed invention). That Bhasale recites a number of alternative binders is immaterial to the obviousness analysis, as it is well settled that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands. Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985). That an alternative embodiment may be described as “encouraged” does nothing to detract from the totality of what the art provides the skilled artisan. Art is art, not only for what it expressly teaches, but also for what it would reasonably suggest to the skilled artisan, including alternative or non-preferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). That a particular embodiment of Bhasale behaves differently from the claimed invention is irrelevant, as Bhasale is not relied upon to establish anything other than the known utility of EUDRAGIT L30D as a pharmaceutical binder useful as a methacrylate copolymer binder per the teachings of Makino.
Applicants continued piecemeal analysis of the prior art next focuses on the JP’83 reference, and they again overlook the fact that the EUDRAGIT copolymers applicants themselves acknowledge provide for the colonic delivery of the present claims were, at the time the instant application was filed, known to be usefully employed as outer enteric coatings for pharmaceutical dosage forms in the same manner Makino, and applicants, employ them as external enteric coatings of pharmaceutical dosage forms.
For at least these reasons, applicants arguments are unpersuasive.
Conclusion
No Claims are allowable.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN M BASQUILL whose telephone number is (571)270-5862. The examiner can normally be reached Monday through Thursday, 5:30 AM to 4 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571) 272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEAN M BASQUILL/Primary Examiner, Art Unit 1614