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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/2/25 has been entered.
Receipt of amendment and response dated 7/2/25.
Claims 2-5, 7-8, 10-11, 14-17, 19-196, 199-200 and 209-237 are canceled.
New claims 254-259 have been added.
Claims 1, 6, 9, 12-13, 18, 197-198, 201-208 and 238-259 are pending for examination.
Claims 238-241 have been withdrawn as being non-elected.
Claims 1, 6, 9, 12-13, 18, 197-198, 201-208, 242-259 have been considered for examination.
In response to the amendment, all of the previous rejections have been replaced with the following new rejections:
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 6, 9, 12, 13, 18, 197-198, 206-208, 246-249 and 252-259 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2009/125432 to Junginger et al (Junginger) (cited on IDS) in view of US 20070009592 A1 to Remon et al., and US 20120301535 to Williams et al (Williams).
Junginger teaches an expandable drug delivery system comprising one or more actives, force generating components, one or more absorption modifiers and one or more bioadhesive polymers (abstract). In a preferred embodiment, Junginger teaches that the expandable delivery system in which the dosage form reaches the desired site of action and imbibe the fluids of the intestinal environment into the core, where it activates the force generating material in the core which creates a force to expand the dosage form. The imbibing action of the dosage form meets the instant drying the region by absorption of the fluids. In one instance, Junginger states that the delivery system with subunit delivery systems is driven by either swellable polymers and/or by the gas (p 9, last para). Junginger teaches that the active agent is a protein and/or peptide drug(s) (abstract). For the claimed active agent (claims 250 and 251), Junginger teaches several biological active agents such as proteins, peptides, including glucagon-like peptide GLP-1 (page 10 and p 11, l 5). Junginger teaches several swellable polymer (pages 12-13) and further teaches inclusion of hydro-attractants that improve the swelling, and include crosslinked polyacrylic acid, crosslinked polyvinylpyrrolidone, crosslinked carboxymethyl cellulose etc (p 14, 1st para).
Example 2 of Junginger describes a composition comprising insulin (active agent) and cross-linked polyacrylic acid, which is covered with an enteric coating. [00102] of the instant specification describes hydrogel polymers that are crosslinked and includes poly(acrylic acid). Thus, cross-linked polyacrylic acid of Junginger meets instant drying agent. Instant claim 197 recites at least 35% by weight and less than about 75% by weight. In this regard, example 2 of Junginger teaches 110 mg/tablet of cross-linked polyacrylic acid. Example 2 of the reference amounts to 289 mg weight of the tablet with an amount of 110 mg of crosslinked polyacrylic acid results in 38% by weight and hence falls within the claimed “a total drying agent content of at least about 35% by weight and less than about 75% by weight”. Claim 198 recites at least about 50% by weight and less than about 75% by weight. While Junginger does not explicitly teach claim 198, the reference suggests employing the swellable polymer such that the polymer swells to 10%, 15%, 50%, 100% or 200% upon ingestion, and therefore one of an ordinary skill in the art would have optimized the amount of the polymer based on the amount of swelling desired.
While Junginger do not explicitly teach the fluid uptake capacity of the composition, drying capacity and drying time as claimed (claims 1, 6, 9, 12, 13,18, 201-208 and 254-255), the reference teaches the same polymer and in the amounts within the claimed range, as that described in the instant specification, and therefore, the fluid uptake capacity of the composition of Junginger meets the instant claimed fluid uptake capacity property of claims 1, 6, 9, 12, 13 and 18. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Further, "when the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Swinehart, 439 F.2d 210, 213, 169 USPQ 226, 228 (CCPA 1971).
For claims 246-249, Junginger further teaches that the composition further includes permeation enhancers such as sodium caprate, to increase the epithelial permeability. Therefore, it would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention to prepare the composition of Junginger with suitable amount of the crosslinked polyacrylamide particles and further include sodium caprate, suggested by Junginger, as a permeation enhancing agent. One of an ordinary skill in the art would have expected to increase the permeability of the oral dosage of Junginger.
For the claimed mixture of the active agent and crosslinked polyacrylic acid (instant drying agent), Junginger teaches that the composition is prepared by granulation technique by step-wise addition and mixing to obtain the granules (P 18, 2nd full para) and compressed. The composition includes the claimed active agent, crosslinked polymer (Ac-Di-Sol). The composition is further coated with a polymer to obtain a smooth coating and further with an enteric coating (p18, 2nd full para).
For the claimed particles, Junginger teaches drug carrier nanosized or microsized particles (page 5, 2nd para, p 6, 2nd para). In this regard, example 2 of Junginger also shows that the crosslinked polyacrylic acid is not stated as being separate from the active agent.
However, Junginger fails to teach the claimed particles, granules or minitablets of the active agent and a mixture of the active agent and the drying agent with the particles maintaining the boundaries.
Remon teaches oral an immediate or fast release pharmaceutical granule composition comprising at least one drug (i) classifiable as Class II or Class IV of the Biopharmaceutical Classification System, wherein the said drug constitutes at least about 0.5% by weight and no more than 50% by weight of the composition, and further comprising , wherein the active agent is admixed with a pharmaceutically acceptable excipient, a blend of microcrystalline cellulose and a swellable polymer, formulated into a granule composition (0024). Remon further teaches that the composition can be in the form of capsule that included the granule composition [0024].
For the first pharmaceutically acceptable excipient, Remon teaches mixing a drug with a blend of microcrystalline cellulose and a swellable polymer, and prepared as a granule composition, and the granules included filled in the capsules. Examples 2 and 3 of Remon describes mixing solid fractions comprising maltodextrin and xanthan gum, with the active agent, fed into the twin screw extruder to prepare granule formulations. Examples 4 and 5 further describes granule preparation of hydrochlorothiazide, PEG 4000, PEG 400 and Avicel PH 101/Avicel CL 611, and described the solid fractions homogenized and the mixture fed into the twin extruder to produce granules.
Further, Williams teaches nanoparticles of a peptide drug incorporated into various dosage forms (abstract), for use in medicines e.g., treating blood glucose regulation [0002]. Williams teaches nanoparticulate insulin and nanoparticulate GLP-1 for enhancing the bioavailability of insulin and/or reducing the pancreatic insulinotropic effect of GLP-1 upon administration of the GLP-1 to a mammalian subject [0017 and 0091]. The nanoparticle Williams teaches inclusion of a water-swellable polymer [0030] in the film and the active agent is dispersed throughout the film.
Therefore, it would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention to prepare the delivery dosage form of Junginger comprising nanoparticles of matrix i.e., crosslinked polyacrylic acid and further incorporate nanoparticles of active agent such as GLP-1, such that the drug and the polymer are mixed as solid particles so as to provide a granule formulation that can be efficiently filled into capsules with an expectation to maintain the drug and polymer particles separately as well as provide the desired bioavailability of the active agent GLP-1. One of an ordinary skill in the art would be motivated to do so because Remon teaches solid granulate formulation prepared by admixing solid drug and pharmaceutically acceptable excipients (such as swellable polymers) as a blend and extrusion enables high loading of the active even when present at low amounts and provides desired dissolution. Further, Williams suggests that nanoparticulate drug provides increased bioavailability of insulin and reduced pancreatic insulinotropic effect of GLP-1.
For claims 256 and 257, Junginger teaches enteric coating over the dosage form (abstract). While Claims 258 and 259 recites drying gent “consisting essentially of”, "A ‘consisting essentially of’ claim occupies a middle ground between closed claims that are written in a ‘consisting of’ format and fully open claims that are drafted in a ‘comprising’ format." PPG Industries v. Guardian Industries, 156 F.3d 1351, 1354, 48 USPQ2d 1351, 1353-54 (Fed. Cir. 1998). For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." See, e.g., PPG, 156 F.3d at 1355, 48 USPQ2d at 1355 ("PPG could have defined the scope of the phrase ‘consisting essentially of’ for purposes of its patent by making clear in its specification what it regarded as constituting a material change in the basic and novel characteristics of the invention.").
For claims 252-253, Junginger teaches that a bioadhesive polymer is an option and, in this regard, Williams and Remon do not teach any bioadhesive polymer or agent as essential. Therefore, one of an ordinary skill in the art would be able to choose to prepare the composition of Junginger (modified with Remon and Williams) with or without a bioadhesive polymer and still achieve the advantage of an expandable drug delivery system.
Claims 242-245 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2009/125432 to Junginger et al (Junginger) (cited on IDS) in view of US 20070009592 A1 to Remon et al., and US 20120301535 to Williams et al (Williams) as applied to claims 1, 6, 9, 12, 13, 18, 197-198, 206-208, 246-249 and 252-259 above, and further in view of Soppirnath et al (European Journal of Pharmaceutics and Biopharmacuetics, 2002, vol. 53: Issue 1, p87-98).
Junginger, Remon and Williams discussed above, do not teach the claimed particle size of cross-linked polyacrylamide (claims 242-245).
Soppirnath teaches crosslinked polyacrylamide grafted hydrogels for preparing microspheres and loaded with drugs (abstract). Soppirnath studied the effect of particle size, swelling behavior and drug loading (p 89, col. 1). Soppirnath teaches that the particles have a mean diameter ranging from 391 to 594 micron and with increasing crosslinking the particle size decreases from 594 to 391 microns (p 93). Further, Table 1 shows the amount of water uptake, drug loading and particle size as a function of cross-linking, and that the tightly crosslinked matrix does not expand in water as much as the loosely crosslinked polymer (col. 2, p 94).
Hence, it would have been obvious for one of an ordinary skill in the art to choose the particles of crosslinked polyacrylamide, (in the teachings of Junginger modified by Remon and Williams), having a suitable size such as that suggested, within the claimed particle size less than 1000 nm (claim 242 and 244) or even less than 200 nm (claims 243 and 245). One of an ordinary skill in the art would have been motivated to do so because Soppirnath teaches that the amount crosslinking controls the particle size as well as drug loading in the crosslinked polymer. While Soppirnath generally suggests a particle size of 594 to 391 microns, one of an ordinary skill in the art would have optimized the crosslinking of the polymer and particle size so as to provide the desired release rate of the active agent because Soppirnath also teaches that tightly cross-linked polymer matrix does not expand much in water as a lightly cross-liked polymer.
Claims 250-251 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2009/125432 to Junginger et al (Junginger) (cited on IDS) in view of US 20070009592 A1 to Remon et al., and US 20120301535 to Williams et al (Williams) as applied to claims 1, 6, 9, 12, 13, 18, 197-198, 206-208, 246-249 and 252-259 above, and further in view of US 20040209801 to Brand et al.
Junginger, Remon and Williams, discussed above, do not teach the claimed the specific agent i.e., an agonist of GLP-1 or a GLP-1/GIP co-agonist. However, Junginger teaches that the drug delivery system can include a number of active agents, and particularly teaches controlled release for diabetic treatment (col. 5, l 1-4).
Brand teaches methods and compositions for treating a diabetic subject with islet neogenesis therapy and an agent for immunosuppression, with formulations and methods for local delivery and for sustained release of the compositions [0002], the method including administering to a mammal a therapeutically effective amount of a composition comprising a gastrin/CCK receptor ligand and a factor for complementing gastrin for islet neogenesis therapy (a FACGINT), provided that the FACGINT is not an EGF receptor ligand. For the FACGINT, Brand teaches at least one selected from the group of: a Glucagon-like peptide 1 receptor ligand; a Glucagon-like peptide 2 receptor ligand [0009, 0011,0051 and 0075]. In particular, Brand teaches exendin, a GLP-1 agonist (0075). Brand teaches oral sustained release systems such as oral osmotic systems [0127] and 0132] and oral administration.
Hence, it would have been obvious for one of an ordinary skill in the art to prepare the composition of Junginger (modified by Remon and Williams) and further include Glp-1 agonist of Brand and further use the composition to treat diabetes because while Junginger teaches the hydrogel polyacrylamide particles comprising composition for providing controlled release delivery of active agents for treating diabetes, Brand suggests effective treatment of diabetes with Glp-1 increases the number of pancreatic insulin secreting beta cells [0017] and thus overcoming the pancreatic exhaustion and insulin insufficiency, which is the cause of diabetes II (0004). A skilled artisan would have expected that GLP-1 agonist in the composition of Junginger provides effective treatment of diabetes II.
Response to Arguments
Applicant's arguments filed 7/2/25 have been fully considered.
In response to the arguments and amendments to claims 252-253, the rejections previously made under 35 USC 112, first and second paragraphs have been withdrawn.
Rejection under 35 USC 103:
Applicants’ arguments regarding Rashid and Grenier have been considered but the present rejections do not rely on the argued references and therefore the arguments are moot.
The present rejection relies on a new combination of references i.e., Junginger in view of US 20070009592 A1 to Remon et al., and US 20120301535 to Williams et al.
Applicants’ argument regarding Junginger have been considered. It is argued that Junginger discloses “gas empowered expandable drug delivery systems” having one or more microparticles, wherein each microparticle acts as a separate delivery system in which the active agent is entrapped”, and example 1 teaches microparticles containing insulin, polyethylene oxide and trimethyl chitosan, the said microparticles are pushed to the mucosal membrane surface by carbon dioxide gas bubbles formed by the composition.
However, Applicants’ arguments are not persuasive because instant claims recite “comprising” and do not exclude “gas empowered expandable drug delivery systems”. Further, the rejection does not rely only on Junginger and instead relies on the new references, Remon and Williams references, for preparing the active agent as microparticles and for preparing a mixture of the active agent and crosslinked polymer (such as polyacrylic acid).
The argument that the teachings of Soppirnath or Brand references do not cure the deficiencies of Rashid is not persuasive because the teachings of Soppinath and Brand have now been combined with a new combination of references and the combination of Soppinath or Brand with Junginger, Remon and Williams address the claimed limitations.
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/LAKSHMI S CHANNAVAJJALA/Primary Examiner, Art Unit 1611