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 Objections
Claims 9 and 11 are objected to because of the following informalities: on line 2 of claims 9 and 11, applicant need to change “the solvent” to --- a solvent ---. Appropriate correction is required.
Claims 26 and 30 are objected to because of the following informalities: in both of claims 26 and 30, on line 4, applicant need to change “and” to --- or --- in front of “(iii) methacrylic acid,”; and on line 5, applicant need to change “zein and” to --- zein or ---. Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
Claim(s) 8, 9 and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Li (CN 101716180 A, its English abstract and its English translation) in view of (i) Tadashi (JP 2712583, its English abstract and its English translation), Furuta (US 2005/0100593 A1) or Tanimoto et al (5,447,732), (ii) Bertuzzi (“Granulation: evolving slowly but surely”, Pharmaceutical Technology Europe, Vol.22 (6) (June 2010), pg. 1-9, obtained from the website: https://www.pharmtech.com/view/granulation-evolving-slowly-surely ) and (iii) Maes et al (US 2008/0274181 A1).
Li teaches (see English abstract) a combined medicament for supplementing zinc and calcium wherein the zinc and calcium are released at different areas of the gastro-intestinal tract. The preparation method for the zinc supplement comprises the steps of: taking zinc gluconate (instant nutritionally acceptable zinc salt of claim 25) and vitamin D; adding medicinal starch and microcrystalline cellulose and mixing; adding crushed superfine silica gel powder and evenly mixing; and sub-packaging into enteric capsules (the enteric capsules teach a solid dosage form with a gastro-resistant outer coating). As stated by Li (see [0031] of English translation), zinc gluconate directly stimulates the stomach and is prone to stomach discomfort, nausea or vomiting and other gastrointestinal irritation symptoms. However, Li’s medicament and its preparation method discussed above ensure that the vitamin D is not damaged in an acid environment and that direct stimulation of the stomach by zinc gluconate is avoided. After patients take the two capsules (one for supplementing zinc and another for supplementing calcium), effective components of the vitamin E and the calcium acetate will be rapidly disintegrated and absorbed in the stomach while the vitamin D and the zinc gluconate will be disintegrated and absorbed in the intestine. Li teaches (see English abstract) that its invention has the characteristics of high bioavailability and low side effect.
With respect to instant amount of the zinc present per solid dosage form, Li teaches (see pg.3, line 82 of machine-assisted English translation) that 8-15 g of zinc are present in 2000 enteric-coated capsules, which gives 4 -7.5 mg per enteric-coated capsule (as calculated by the Examiner). Such range for the amount of zinc falls within instant range of claim 8 (about 1-75 mg) as well as instant range of claim 24 (about 1-50 mg) for the amount of zinc per solid dosage form, thus teaching instant ranges of claim 8 and claim 24.
Li does not teach using instant poly--glutamic acid in its medicament containing zinc gluconate. However, as evidenced by Tadashi et al (see English abstract and pg.2 of machine translation (the paragraph under [Means for Solving Problems]), Furuta ([0007], [0008], [0021], [0022] and [0033]) or Tanimoto (col.2, lines 52-58 and claim 14), poly-gamma-glutamic acid is already known in the art as a mineral absorption promoter capable of solubilizing minerals (including zinc) in intestinal tracts and accelerating intestinal absorption of minerals (including zinc). Since Li wants to ensure that zinc gluconate is absorbed in the intestine, it would have been obvious to one skilled in the art to add poly-glutamic acid into Li’s medicament containing zinc gluconate so as to further ensure that direct stimulation of the stomach by zinc gluconate is avoided and that zinc gluconate is more effectively absorbed (with the help of poly-gamma-glutamic acid) in the intestine.
As to instant range for the molecular weight for the poly-glutamic acid, Furuta ([0022] and [0033]) indicates that poly--glutamic acid should have molecular weight of 3,000-1,000,000 (which is 3kDa-1,000 kDa) in order to obtain effects of dissolution and acceleration of intestinal absorption of minerals (such as zinc, calcium, iron, magnesium and copper). Tanimoto also indicates (col.6, lines 9-20 and claim 14) that the molecular weight of the poly-glutamic acid should range 10,000-300,000 in order to achieve acceleration of the absorption of minerals (such as zinc) in a human. Both of those molecular weight ranges taught by Furuta and Tanimoto overlap with instant ranges of claim 8 and claim 23, thus rendering instant ranges prima facie obvious. In the case “where the [claimed] ranges overlap or lie inside ranges disclosed by the prior art,” a prima facie case of obviousness would exist which may be overcome by a showing of unexpected results, In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Thus, Li in view of Tadashi, Furuta or Tanimoto teaches a solid dosage form (enteric coated capsule) comprising gamma-polyglutamic acid and a zinc salt. Li’s capsule does not teach instant tablet with a gastro-resistant outer coating as claimed in claim 8. However, Li teaches ([0020]) that other suitable dosage forms, such as tablets, may be used in its invention. It would have been obvious to one skilled in the art to make Li’s formulation (as modified by the teachings of Tadashi, Furuta or Tanimoto) containing gamma-polyglutamic acid and a zinc salt into a tablet (instead of a capsule) with a reasonable expectation of success.
Li does not teach a method for preparing tablets. However, it is well known in the art, as evidenced by Bertuzzi (see pg.4, 2nd paragraph under “Future needs”), that tablets represent a majority of dosage forms sold worldwide. Tablets are often made of granules and consequently, the granulation process plays a major role in the production of high-quality medicines. Bertuzzi further teaches (pg.2, last paragraph and pg.3, first paragraph) that despite of its many steps and high production cost, wet-granulation is the most widely used technology for granulation because it is the most flexible granulation technology available (it can handle the majority of formulations). Based on Bertuzzi’s teaching, it would have been obvious to one skilled in the art to produce Li’s tablet (as modified by Tadashi, Furuta or Tanimoto) by using a wet granulation process with a reasonable expectation of success.
Bertuzzi does not teach the details of the wet granulation or tableting. Maes teaches ([0251]) that in the wet granulation process, an active ingredient powder is agitated (mixed) in the presence of a liquid (solution binder) followed by drying. For forming the granules which are eventually to be compressed into the tablet cores, the drug (active ingredient) is first granulated with a solution binder in a granulator (such as a fluidized bed granulator or high shear mixer). The solution binder is formed by first dissolving or dispersing the binder in a suitable solvent (see [0247] – the binder is added to a drug-filler mixture to increase the mechanical strength of the granules and tablets during formation). The solution binder is then top-sprayed into the drug in a granulator. If necessary, additional excipients (fillers) can be mixed with the drug (active ingredient) prior to the granulation step. Thus, Maes teaches instant steps (a) and (b) of claim 8. Maes further teaches ([0252]) that the formed granules are subsequently dried and sieved. The sieved granules are then blended with a lubricant (and optionally a glidant). The blended granules are subsequently pressed using, for example, a rotary press to form tablet cores. Thus, Maes teaches instant (c) and (d) of claim 8. With respect to instant step (e), Maes further teaches ([0255]) that the tablet may be coated and the tablet cores are coated with a controlled release coating which may be an enteric coating (see [0039], [0040] and [0204]). Since Li teaches that direct stimulation of zinc gluconate to the stomach should be avoided and that zinc gluconate should be absorbed in the intestine, it would have been obvious to one skilled in the art to coat the tablet core (containing gamma-polyglutamic acid, zinc gluconate and vitamin D) with an enteric coating (instant step (e) of claim 8) so as to ensure the delivery of the active ingredients to the intestine.
Thus, in view of (i) Tadashi, Furuta or Tanimoto, (ii) Bertuzzi and (iii) Maes renders obvious instant claims 8 and 23-25.
With respect to instant claim 9, Maes teaches ([0474]) that in wet granulation, water or aqueous solutions are employed. Alcohols, typically ethanol or isopropanol, can be included with the granulating water to enhance the workability of the granulation. It would be obvious to one skilled in the art to use aqueous solution of ethanol as the granulating liquid with a reasonable expectation of enhancing the workability of the granulation. As to “less than about 10 wt% water content”, Maes gives an example (see [0254]) of the wet granulation process where the granules are dried until the loss on drying (“LOD”) is below 1%. Under such guideline, instant limitation “less than about 10wt% water content” would have been obvious to one skilled in the art before the effective filing date of the claimed invention since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233. Thus, in view of (i) Tadashi, Furuta or Tanimoto, (ii) Bertuzzi and (iii) Maes renders obvious instant claim 9.
With respect to instant claim 26, Maes teaches ([0207]) that its enteric coating material can be chosen from cellulose acetate phthalate, cellulose acetate succinate, hydroxypropyl methylcellulose phthalate (instant hypromellose phthalate), hydroxypropyl methylcellulose acetate succinate (instant Hypromellose acetate succinate) and a copolymer of methyl acrylate/methacrylic acid. It would be obvious to one skilled in the art to choose one of these materials as the enteric coating material to coat the tablet core of Li (as modified by Tadashi, Furuta or Tanimoto) with a reasonable expectation of success. Thus, in view of (i) Tadashi, Furuta or Tanimoto, (ii) Bertuzzi and (iii) Maes renders obvious instant claim 26.
Claim(s) 10, 11 and 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Li (CN 101716180 A, its English abstract and its English translation) in view of (i) Tadashi (JP 2712583, its English abstract and its English translation), Furuta (US 2005/0100593 A1) or Tanimoto et al (5,447,732), (ii) Bertuzzi (“Granulation: evolving slowly but surely”, Pharmaceutical Technology Europe, Vol.22 (6) (June 2010), pg. 1-9, obtained from the website: https://www.pharmtech.com/view/granulation-evolving-slowly-surely ), (iii) Maes et al (US 2008/0274181 A1) and (iv) Marvola et al (“Enteric polymers as binders and coating materials in multiple-unit site-specific drug delivery systems”, European Journal of Pharmaceutical Sciences, vol.7 (1999), pg.259-267).
With respect to instant claims 10, 11 and 27-30, for the reasons already explained above, Li in view of (i) Tadashi, Furuta or Tanimoto, (ii) Bertuzzi and (iii) Maes teaches instant claims 10, 11 and 27-30 except for instant gastro-resistant binder (mentioned in step (a) of claim 10). Marvola teaches (see abstract) teaches that drug release can be targeted on the distal part of the small intestine and the colon by preparing film-coated matrix pellets, in which enteric polymers (such as methacrylate polymers, hydroxypropyl methylcellulose acetate succinate and cellulose acetate phthalate) dissolving at pH of approximately 7 are used as both as binders in the pellets and as coating material. Since Li seeks to ensure that zinc gluconate is absorbed in the intestine, it would be obvious to one skilled in the art to use the enteric coating material (which is used for coating the tablet core) also as a binder in the tablet core of Li with a reasonable expectation of targeting the release of the active ingredient on the distal part of the small intestine and the colon. Thus, Li in view of (i) Tadashi, Furuta or Tanimoto, (ii) Bertuzzi, (iii) Maes and (iv) Marvola renders obvious instant claims 10, 11 and 27-30.
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/SIN J LEE/Primary Examiner, Art Unit 1613 May 2, 2026
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