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 .
Claim Status
Claims 1-6 and 8-21 are pending.
Claim 7 has been canceled.
Claims 14-19 are withdrawn.
Claims 1, 3, 8-9 and 13 are currently amended.
Claim 21 has been added.
Claims 1-6, 8-13 and 20-21 are currently under consideration.
Claims 1-6, 8-13 and 20-21 are rejected.
Acknowledgement of Receipt
This Office Action is in response to the Applicants’ amendments and remarks filed 08/14/2025.
Information Disclosure Statement
The Information Disclosure Statement(s) (IDS) submitted on 01/08/2025 and 08/14/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, this IDS has been considered by the Examiner.
Withdrawn Rejections
In light of the removal of the terms and/or phrases: substantially, at least a portion of, over time, at least about, in the claims 1, 3, 8-9 and 13, the rejection of claims 1, 3, 8-9 and 13 under 35 U.S.C. § 112(b) as being indefinite is withdrawn.
New Rejections
Applicant’s amendments have necessitated the following grounds of rejection:
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 (a) are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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. Applicants are 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.
Claim(s) 1, 6, 8-13 and 20-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang (US 20220257780 A1, filed 10/07/2020) evidenced by Villagran (US 20170360865 A1, pub. 12/21/2017), and Soane (US 20210113476 A1, pub. 04/22/2021) evidenced by Nishii (US 6,517,870 B1, pub. 02/11/2003).
Wang discloses a pharmaceutical composition for oral administration, comprising micronized ion-exchange resin particles having particle sizes less than 50 μm, and at least one therapeutic agent releasably bound to the micronized resin particles through ionic interaction to form resin-therapeutic agent complexes (abstract, [0010], claim 1) in response to the strong need for developing age-appropriate formulations, such as formulations for pediatric and geriatric patients, with improved palatability and uniformity ([0009]).
Regarding the 1 µm to about 200 µm limitation, Wang discloses that the particle size of the resin-therapeutic agent complex is from about 0.5 μm to about 40 μm ([0022]). MPEP 2144.05 states that a prima facie case of obviousness exists in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art.
Regarding the “as measured by a particle analyzer using laser diffraction,” limitation, the Examiner notes that this recitation does not give patentable weight.
Regarding the recitation of unit dose form, Wang discusses how the uniformity of the formulation affects accurate unit dosage ([0073]). Particularly when administering children, dosage in the form of emptying capsule contents and then mixing in soft foods is problematic because there can be loss or an incomplete dose ingestion ([0074]). As the resin-therapeutic agent complexes have particle sizes less than 50 μm, and the pharmaceutical composition is formulated as a dosage form having uniform dispersion of the resin-therapeutic agent complexes, a reduced gritty mouthfeel results which is particularly important for geriatric patients and pediatric patients, especially neonates and infants. More accurate dosing and substantial taste masking is provided, thus giving an effective strategy for developing age-appropriate formulations, especially for pediatric and geriatric patients ([0076]); particularly important in cases when flexible-dose adjustment is required to assure therapeutic benefit and minimize adverse effect, such as NPI drugs that require dose adjustment according to patient medical conditions (e.g., impaired liver or kidney functions), for individualized treatment, such as pediatric treatment in ICU, and for any situation when individualized dosing is required ([0077-0078]).
Regarding the unit dose form is ingestible, Wang teaches that the pharmaceutical composition containing the disclosed micronized resin-therapeutic agent complex may be stored for future use or promptly formulated with conventional pharmaceutically acceptable carriers to prepare finished ingestible compositions for delivery orally, nasogastric tube, or via other means and may take the form of solid preparations such as gels ([0117]). Wang teaches that the dosage form can be one of suspension, dry powder for suspension, orally disintegrating tablets, mini-tablets with the longest dimension less than or equal to 3 mm, chewable tablets, oral jelly, and oral gummies ([0015], [0037], [0114], claim 4). Here Wang teaches a gummy as a unit dose form that is ingestible.
Regarding spray drying, metformin, and coating material species limitations, spray drying is taught as a process as a means of collecting particles ([0153]), metformin as an example of a therapeutic agent ([0108]), and hydroxypropyl methylcellulose (HPMC) as a diluent or carrier, binder and adhesive, dispersing agent, thickener, viscosity enhancing agent ([0014], [0036], [0087], [0119], [0157], [0160], claim 3). While Wang teaches further treatment of the ion exchange resin with a release retardant and diffusion barrier coating to maximize the safety for pharmaceutical use or for improved performance of the compositions ([0100]), and that the resin-therapeutic agent complexes can be further processed, together with suitable excipients (binder, filler, disintegrant, glidant, lubricant, coating, colorant, flavors, etc.), using suitable manufacturing processes (blending, granulation, compression, coating, Wurster coating, extrusion-spheronization etc.) ([0158]), encapsulation of the particles in the coating material comprising metformin is not explicitly taught. Examiner further points to evidence from Villagran in which extrusion processes are well-known processes in the art ([0157-0158], [0166]) and are utilized to form soft chewable ingestible compositions that can contain an active ingredient such as metformin ([0120]), into any suitable convenient, ingestible form which include gummies ([0180]).
Soane is provided to explicitly teach the coating material limitation.
Soane discloses an orally ingestible delivery system for releasing a therapeutic agent within an intestine of a mammal, comprising a permeable capsule system is dimensionally adapted for oral ingestion (title, abstract, [0002], [0016], claim 1). Soane focuses on improving bioavailability given the conditions in the stomach (i.e., hydrolysis by stomach acid) ([0008]).
Excerpts from paragraph [0234] of Soane are provided below.
In embodiments, therapeutic agents used with the orally ingestible delivery systems can be further coated (e.g., with enteric coatings) to delay release of the therapeutic agent even after it has been released from the delivery system. Typically, extended release dosage forms are formulated in such a manner as to make the therapeutic agent available over an extended period of time following administration. Extended release dosage forms can be further characterized as sustained release or controlled release. Sustained release systems maintain the rate of drug release over a prolonged period of time. Sustained release dosage forms can permit the therapeutic agent to release gradually, for example, along the entire small intestine, resulting in a prolonged period for absorption and a consequent prolonged interval of drug concentration in the therapeutic range. Sustained release dosage forms commonly use various polymers that coat granules or tablets, or that form a matrix within which the drug is dissolved or dispersed. Additives and formulations to facilitate sustained or controlled release are well-known in the art. For example, polymeric materials such as hydroxypropyl methylcellulose or other cellulose ethers can be used for formulation. Dosage forms can be formulated with enteric coats to tune sustained release. The combination of two therapeutic agents in one form factor can achieve bimodal pharmacokinetic release of the two agents, as required by a patient's treatment plan. Alternatively, or in addition, an external enteric coating can be provided that dissolves more distally in the intestine, allowing delayed release. In embodiments, a combination of therapeutic agents can be combined as the therapeutic agent deliverable for delivery by the orally ingestible delivery system, where the combination of therapeutic agents is complementary or synergistic. For example, a combination of treatment agents can be provided for treating diabetes and other glucose regulation disorders, for example a peptide like an incretin (e.g., exenatide) and a small molecule like a biguanide compound (e.g., metformin) ([0234]).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to apply coating taught by Soane to the particles of Wang with expected results. One would be motivated to do so with a reasonable expectation of success as the dispersible acid barrier ([0016-0017]) of Soane facilitates an improved delivery vehicles that can be optimized for easy ingestion, for example in palatable and easy-to-eat dosage forms or milieus and that pharmaceutical products in edible forms are well-known in the art, for example ‘gummies,’ ([0011]). Soane teaches and suggests that the improved consistency and flavor of the delivery vehicle improves its overall acceptance by patients especially for populations that are reluctant to or unable to swallow pills. Soane suggests that it would be further advantageous to provide the delivery vehicles in a food item that facilitates ingestion. For example, a delivery vehicle that could be added to liquid, gel, or semi-solid media such as soups, drinks, milk shakes, ice cream, yogurt, jellies, and the like, would be appealing to consumers and easy to swallow. Such improved delivery mechanisms would be particularly desirable for those conditions that require frequent dosing, or in specialized populations such as children or patients with dysphagia, because of increased patient convenience and acceptance and decreased complexity and health care cost ([0011]). These teachings complement the objective of Wang which is to provide well controlled batches to minimize their effect on drug content uniformity (see Wang, [0278], [0283]) and enhance drug palatability (Wang, [0008]). Specifically with respect to drug palatability and the drug metformin itself, Nishii provides evidence of bitterness and irritation experienced when taking a biguanide drug in which oral preparations thereof are in the form of gum drops (i.e., gummy) preferably not tablets; wherein the biguanide is metformin (title, abstract, col. 2, line 37-39; claims 3, 8).
Regarding claim 6, Wang teaches that the co-milling adjuvants are inert, non-toxic pharmaceutical excipients to include polyvinylpyrrolidone (PVP) (i.e., a povidone) that function as a carrier and/or stabilizer of the drug in the milled product to deter agglomeration ([0142]). Soane teaches pectin and carrageenan to increase structural stability and integrity ([0159]).
Regarding claim 8 (i.e., controlled release), Wang discusses at great length about sustained release or controlled release in paragraph [0234].
Regarding claim 9 (i.e., particles are homogeneous), Wang discloses that according to one aspect of this disclosure, ion-exchange resin particles may be subject to a size reduction process (e.g., milling, homogenization) to obtain micronized resin particles with particle sizes less than or equal to 50 μm ([0090]). Wang also teaches the production of particles using known in the art high pressure homogenization techniques ([0143]).
Regarding claims 10 (i.e., excipient), 11 (i.e., carbohydrate, elected species), and 12 (i.e., lactose), Wang teaches suitable excipients to include flavoring agents ([0016], claim 5) and sweeteners: fructose, mannitol, lactose, and sucrose ([0036], [0087], [0126], [0157], [0160]) which are known carbohydrates.
Regarding claim 13, (i.e., retaining metformin), looking to Applicants’ instant specification, the limitation appears to be a property/functional limitation that is tethered to and definitive of the instantly encompassed composition limitation discussed therein (see Spec., [4], [105], [242]). Consistent with MPEP §2111.01(IV), §2112.01(I) and (II), and §2173.05(g), the Examiner submits that where Applicants define composition limitations that are disclosed in the prior art, the recited limitations of claim 13 will also be considered met.
Regarding claim 20 (i.e., a kit comprising the gummy pharmaceutical composition and a container), Wang teaches that in some embodiments, packs/kits include other components, e.g., a metered dose apparatus/device, instructions for dilution, mixing and/or administration of the product, other containers, nasogastric tubes, etc. Other pack/kit components will be readily apparent to one of ordinary skill in the art ([0132]). In addition, Soane teaches packets embedded within the matrix and that a “packet” can be formed integrally from the substance itself, or it can be formed as a capsule, envelope, or other container within which the substance is contained ([0202]).
Regarding claim 21 (i.e., gummy pharmaceutical composition is a food), Applicants describe metformin particles can be administer in the form of a food (e.g., gummy) ([0103]). As mentioned above, Wang discloses oral gummies (claim 4). Soane teaches that any ingestible form factor can be employed, and any consistency suitable for ingestion can be selected. For example, the matrix can be formed into a plurality of gelatinous spheres that can be swallowed in a liquid, such as a syrup or a drink. As another example, the matrix can be formed into an appealing shape for ingestion, like a gum drop or gummy bear, which can be chewed or swallowed whole. Soane provides an embodiment (system 1400) that can be adapted for addition to virtually all food items (e.g., yogurt, cold soups, salads, jams, jellies, flavoring pastes, condiments, and the like), and virtually all drinks (e.g., ice tea, ice coffee, milk shakes, fruit juices, and the like) ([0195]).
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, Soane, with evidence from Villagran and Nishii as applied to claims 1, 6, 8-13 and 20-21 above, in view of Peterman (WO 2020/117736 A1, pub. 06/11/2020).
Regarding claims 2 (i.e., hydroxypropyl methylcellulose acetate succinate (HPMCAS)), while Wang and Soane teach cellulose ether derivatives (Wang [0118], Soane [0159], [0196], [0199]), HPMCAS is not explicitly taught.
Petermann discloses a hydroxypropyl methylcellulose acetate succinate (HPMCAS) with high molecular weight useful for preparing solid dispersions, coated dosage forms, capsule shells and hydrogels (abstract). HPMCAS polymers which have a high molecular weight are taught as being efficiently used in spray-drying and coating processes (pg. 2, lines 5-7). Petermann explicitly teaches a solid dispersion comprising at least one active ingredient and the HPMCAS (pg. 4, lines 25-27; claim 7) and a coated dosage form wherein the coating comprises the HPMCAS (claim 8).
Regarding claim 3 (i.e., enteric coating), Petermann teaches that although HPMCAS polymers are very useful and widely used as enteric polymers for the production of hard capsules, tablet coatings or as a matrix polymer in tablets, there is an urgent need to find new dosage forms for active ingredients. Some people have difficulties to swallow tablets or capsules, for example elderly people or children. The administration of tablets or capsules to pets or other animals is also difficult. Therefore, chewable gels, also designated as gummies or pastilles, are also used as pharmaceutical or nutritional dosage forms (pg. 3, lines 13-19).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to apply the HPMCAS taught by Petermann in the compositions taught by Wang and Soane with expected results. One would be motivated to do so with a reasonable expectation of success because Petermann provides a high molecular weight polymer that is highly desirable due to its known good resistance against simulated gastric juice (abstract, pg. 4, lines 15-16) to suggests enhance patient safety and compliance and improved bioavailability.
Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, Soane, with evidence from Villagran and Nishii as applied to claims 1, 6, 8-13 and 20-21, in view of Heiman (WO 2015/200842 A1, pub. 12/30/2015).
Regarding claim 4 (i.e., 100 mg to about 3000 mg), and claim 5 (i.e., 500 mg to about 2500 mg), Wang and Soane do not teach these amounts for metformin.
Heiman teaches pharmaceutical compositions and methods of using metformin and a microbiome modulator in pharmaceutical compositions for the treatment of diabetes that ameliorate the negative side effects normally encountered in human patients administered the currently available metformin formulations (title, abstract, [0002], claim 1). Heiman teaches that the pharmaceutical composition is formulated as an oral unit dosage form (claims 40, 42-43).
Heiman teaches that the pharmaceutical composition may be formulated for oral administration; may be formulated as be formulated as a liquid formulation, tablet, pill, capsule, pellet, intravenous solution, or any formulation known to one of skill in the art. For example, the composition may be formulated as a medical food. The composition may also be formulated as an edible product, such as: yogurt, a gummy snack such as a gummy bear, licorice, a food bar, a breakfast bar, an edible bar with a semisolid or gelatinous center, a milkshake, a smoothie, pudding, Jell-O™, a dessert preparation, a yogurt material packaged in a small tube for individual serving as with Go-Gurt™, and any other edible composition known to one of skill in the art ([0026]). In an Edible Product Formulation of Metformin-MB Heiman teaches gummy snack, e.g., gummy bear with the doses of metformin typically needed in a range from 500 mg – 1000 mg ([0115]; [0125], see single doses in Table 1). The therapeutically effective amount of metformin may comprise from about 100 mg to about 1000 mg per dose ([0037]); 500 mg per dose, 750 mg per dose, 850 mg per dose, and 1000 mg per dose ([0038]). MPEP 2144.05 states that a prima facie case of obviousness exists in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art.
Response to Arguments
Applicants’ arguments with respect to claims 1-13 and 20 have been considered but are moot because the because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicants argue that the Office failed to provide evidence from the cited references for the assertion that extrusion relates to the term gummy (Remarks, pg. 6, para. 2). Applicants argue that as Chen teaches the preparation pellets, the cited prior art is deficient in providing a dose, nor the gummy that is in unit dose form (pg. 6, last para.).
With respect to the citing of MPEP 2143.03, the Examiner agrees that all words in a claim must be considered in judging the patentability of that claim against the prior art. As such, Applicants’ amendments further limit the claim by now reciting, “in unit dose form” wherein the composition in unit dose form “is ingestible.” Considering these words in the claim, gummy is now further defined; the definition as narrowed. Regarding Applicants’ argument about extrusion disclosed in the cited prior art, the Examiner further points to evidence from Villagran in which extrusion processes are well-known processes in the art ([0157-0158], [0166]) and are utilized to form soft chewable ingestible compositions that can contain an active ingredient such as metformin ([0120]), into any suitable convenient, ingestible form which include gummies ([0180]).
Applicants argue that since Chen, Clevenger and Cross are directed to unique dosage forms with unique formulation requirements (pg. 7, para. 3-4, pg. 8, para. 1).
Chen teaches a metformin hydrochloride enteric-coated sustained-release delivery system (abstract, [0017-0018], [0035-0036], claim 1) in which enteric layer comprises and enteric material ([0006]); hydroxypropyl methylcellulose (HPMC) is taught as sustained-release material ([0007], [0024] see Formulation, claim 2). Clevenger was brought in to teach particle diameter range in which the core can comprise a pellet prepared by controlled-spheronization (pg. 25, lines 2-6). Cross provided evidence of milled lactose facilitating a more controlled diameter ([0095]). Combining the cited references is proper given that each one is focused on enhancing controlled delivery of the active ingredients. MPEP 2145(X.)(D.)(1.) states that a known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use. In this case, no evidence has been provided to show of unexpected results.
For these reasons, Applicants’ arguments are found unpersuasive.
Conclusion
All claims under consideration remain rejected; no claims are allowed. Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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.
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/Karen Ketcham/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614