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 .
Withdrawn Rejections:
Applicant's amendments and arguments filed on 01/05/2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
The application is examined in view of sodium alginate with G content less than 50% and viscosity less than 200 mPa.s in a 1% aqueous solution at 20°C; lovastatin as specific active ingredient.
Claims 1, 4, 8, 11-13, 19 and 21-23 read on the elected species and are under examination; claims 10, 18 and 20 do not read on the elected species and are withdrawn from consideration.
Claims 1, 4, 10-23 are pending, claims 1, 4, 8, 11-13, 19 and 21-23 are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/05/2026 is being considered by the examiner.
Claim Objections
Applicant is advised that should claim 4 be found allowable, claim 22 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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 of this title, 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 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.
Claims 1, 4, 8, 11-13, 19 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Nakamichi et al. (US5456923) in view of Haber et al. (US20090186107) and Chen et al. (US6383471) evidenced by LChen (“Hydrogel / Polymer Micelles Composites Derived from Polymerization of Microemulsions for Oral Drug Delivery”, Ph.D. Dissertation, University of Akron, 2013).
For compact prosecution purpose, additional active ingredient species nifedipine is examined.
Determination of the scope and content of the prior art
(MPEP 2141.01)
Nakamichi et al. teaches a process for producing a solid dispersion (abstract). A process for producing a solid dispersion of a drug dissolved or dispersed in a polymer carrier or diluent which comprises passing a mixture comprising said drug and said polymer through a twin screw compounding extruder having retaining barrels, with said twin screw compounding extruder being equipped with paddle means on each of two screw shafts, whereby said mixture passes between said paddle means and is sheared and compounded thereby, and operating said twin screw extruder while sufficiently heating the barrels to obtain an extrudate in the form of said solid dispersion and wherein said heating is to a temperature below the decomposition temperature of the drug or polymer (claim 1). The polymer includes sodium alginate (claims 4 and 10). The drug includes nifedipine (column 4, line 1-5). The compounding ratio of the drug to the polymer should vary with the species of drug and of polymer, the objective, film characteristics and so on. Based on each part of the drug, the proportion of the polymer is generally 0.1 to 999 parts, preferably 0.5 to 500 parts and for still better results, 1 to 50 parts (column 3, line 10-15). Plasticizer may be included but not required (column 3, line 45-60), as demonstrated in example 1 (column 6), examples 6-7 (column 7).
Haber et al. teaches an orally administrable mucoadhesive film which comprises one or more bioactive ingredients and, as a major film-forming polymer, at least one alginate which is capable of forming a low viscosity aqueous solution (abstract). Films are matrix system, where bioactive agent (BAS) are dispersed in polymer, where release of BAS is due to the diffusion of BAS out of the matrix and/or due to the disintegration of the Matrix (page 1, [0004]). In one embodiment, solid dispersion extrusion is used to prepare film (page 2, [0034]). The films provided by the present invention contain sodium alginate capable of forming a low viscosity aqueous solution as the major film-forming polymer (page 4, [0057]). The table below lists five alginates available from three manufacturers, which alginates were found to be suitable in forming the films of the invention. The viscosity values refer to 1 % (w/v) aqueous solution of the alginate, and were determined by means of Brookfield viscometer (RVT or LV) under the conditions specified below (page 5, [0057]).
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Chen et al. teaches A pharmaceutical composition comprising a hydrophobic therapeutic agent having at least one ionizable functional group and an intrinsic water solubility of less than about 1% by weight such as phenytoin, or lovastatin and a carrier (claims 1-2 and 4). In one embodiment, the composition is in the form of solid dispersion (claim 65).
LChen teaches sodium alginate and their properties (page 46, Table 3-2).
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Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Nakamichi et al. is that Nakamichi et al. do not expressly teach sodium alginate with G content less than 50% and viscosity less than 200 mPa.s and lovastatin. This deficiency in Nakamichi et al. is cured by the teachings of Haber et al. and Chen et al.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Nakamichi et al., as suggested by Haber et al. and Chen et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to use Protanal LF 10/60 LS as sodium alginate for solid dispersion because they are suitable sodium alginate for dispersing active agent as suggested by Haber et al. MPEP 2144.07. Therefore, it is obvious for one of ordinary skill in the art to use Protanal LF 10/60 LS as sodium alginate for solid dispersion and produce instant claimed invention with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to prepare lovastatin as active agent in solid dispersion in Nakamichi et al. because lovastatin is water solubility of less than about 1% by weight and suitable drug for solid dispersion as suggested by Chen et al. MPEP 2144.07. Therefore, it is obvious for one of ordinary skill in the art to prepare lovastatin as active agent in solid dispersion of Nakamichi et al. and produce instant claimed invention with reasonable expectation of success.
Regarding the limitation of consisting essentially of in claim 1 and consists of in claim 23, Nakamichi et al. teaches the solid dispersion only has drug and sodium alginate.
Regarding sodium alginate with G content less than 50% and viscosity less than 200 mPa.s, prior art teach Protanal LF 10/60 LS with G content 40% and viscosity less than 200 mPa.s, as evidenced by LChen.
Regarding the weight ratio of active agent to alginate, prior art teaches the ratio of 1:1 to 1:50, encompassing claimed range 1:3 to 1:5 (1:4).
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In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 4, 8, 11-13, 19 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Miyamoto et al. (US6462093) in view of Haber et al. (US20090186107) and Chen et al. (US6383471) evidenced by LChen (“Hydrogel / Polymer Micelles Composites Derived from Polymerization of Microemulsions for Oral Drug Delivery”, Ph.D. Dissertation, University of Akron, 2013).
For compact prosecution purpose, additional active ingredient species nifedipine is examined.
Determination of the scope and content of the prior art
(MPEP 2141.01)
Miyamoto et al. teaches A method for producing a solid dispersion of a sparingly water-soluble medical substance comprising a sparingly water-soluble medical substance, an amorphous state-inducing agent and an amorphous state stabilizing
agent such as sodium alginate, wherein a weight ratio of the sparingly water-soluble medical substance, the amorphous state-inducing agent and the amorphous state-stabilizing agent is 1:(0.1-10):(0.1-10) (claims 1, 5 and 9). In the case of high-frequency heating, the amorphous state-inducing agent is not an essential component. Sort and
rate of compounding the other two components, (1) the sparingly water-soluble medical substance and (3) the amorphous state-stabilizing agent, are generally (1):(3)=1: (0.1-10), preferably the (1):(3) being 1:(0.3-8), more preferably the (1):(3) being 1:(0.5-5) though they are appropriately selected depending on the sparingly water soluble medical substance to be used (column 7, line 45-55). Examples of the sparingly water-soluble medical substances include dihydropyridine compounds such as nifedipine, nicardipine, hydrochloride, or the like, phenacetin, digitoxin, diazepam, phenytoin, tolbutamide, theophylline, griseofulvin, chloramphenicol, and the like (column 3, line 9-22).
Haber et al. teaches an orally administrable mucoadhesive film which comprises one or more bioactive ingredients and, as a major film-forming polymer, at least one alginate which is capable of forming a low viscosity aqueous solution (abstract). Films are matrix system, where bioactive agent (BAS) are dispersed in polymer, where release of BAS is due to the diffusion of BAS out of the matrix and/or due to the disintegration of the Matrix (page 1, [0004]). In one embodiment, solid dispersion extrusion is used to prepare film (page 2, [0034]). The films provided by the present invention contain sodium alginate capable of forming a low viscosity aqueous solution as the major film-forming polymer (page 4, [0057]). The table below lists five alginates available from three manufacturers, which alginates were found to be suitable in forming the films of the invention. The viscosity values refer to 1 % (w/v) aqueous solution of the alginate, and were determined by means of Brookfield viscometer (RVT or LV) under the conditions specified below (page 5, [0057]).
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Chen et al. teaches A pharmaceutical composition comprising a hydrophobic therapeutic agent having at least one ionizable functional group and an intrinsic water solubility of less than about 1% by weight such as phenytoin, or lovastatin and a carrier (claims 1-2 and 4). In one embodiment, the composition is in the form of solid dispersion (claim 65).
LChen teaches sodium alginate and their properties (page 46, Table 3-2).
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Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Miyamoto et al. is that Miyamoto et al. do not expressly teach sodium alginate with G content less than 50% and viscosity less than 200 mPa.s and lovastatin. This deficiency in Miyamoto et al. is cured by the teachings of Haber et al. and Chen et al.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Miyamoto et al., as suggested by Haber et al. and Chen et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to use Protanal LF 10/60 LS as sodium alginate for solid dispersion because they are suitable sodium alginate for dispersing active agent as suggested by Haber et al. MPEP 2144.07. Therefore, it is obvious for one of ordinary skill in the art to use Protanal LF 10/60 LS as sodium alginate for solid dispersion and produce instant claimed invention with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to prepare lovastatin as active agent in solid dispersion in Miyamoto et al. because lovastatin is water solubility of less than about 1% by weight and suitable drug for solid dispersion as suggested by Chen et al. MPEP 2144.07. Therefore, it is obvious for one of ordinary skill in the art to prepare lovastatin as active agent in solid dispersion in Miyamoto et al. and produce instant claimed invention with reasonable expectation of success.
Regarding “consisting essential of”, 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.". MPEP 2111.03 III.
Regarding sodium alginate with G content less than 50% and viscosity less than 200 mPa.s, prior art teach Protanal LF 10/60 LS with G content 40% and viscosity less than 200 mPa.s, as evidenced by LChen.
Regarding the weight ratio of active agent to alginate, prior art teaches the ratio of 1:(0.5-5), encompassing claimed range 1:3 to 1:5 (1:4).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Argument:
Applicants argue that there is no teaching of picking sodium alginate among other polymers.
In response to this argument: this is not persuasive. Nakamichi et al. teaches sodium alginate among other less than 30 polymers (column2 and claims 4 and 10), and one artisan in the art knows how to choose sodium alginate among other less than 30 polymer because each polymer including sodium alginate is obvious no matter how many other polymer recited, and the recitation of other polymer does not make any particular polymer including sodium alginate less obvious. Thus, the 103 rejection is still proper.
Applicants argue there is no teaching of ratio between drug and solidum alginate.
In response to this argument; this is not persuasive. As discussed in the above 103 rejection, Nakamichi et al. teaches clearly weight ratio of active agent to alginate from 1:1 to 1:50, encompassing the claimed range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Thus, the 103 rejection is still proper.
Applicants argue about unexpected results of Table 3.
In response to this argument: this is not persuasive. Applicant’s data is not sufficient to overcome the 103 rejection at least for the following reasons. Firstly, applicants do not have sufficient number of test in and outside of claimed range, for example, not test of drug polymer ratio of 1:6. MPEP 716/02(d) II, To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960. Secondly, applicant’s data are not significant enough as unexpected. MPEP 761.02 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. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant’s data are provided without standard deviation, and those data are very close and may be not different from each other if error bar are provided and included. Therefore, no unexpected results has been established and the 103 rejection is still proper.
MPEP 2141 III states: “The proper analysis is whether the claimed invention would have been obvious to one of ordinary skill in the art after consideration of all the facts.” Respectfully, after weighing all the evidence, the Examiner has reached a determination that the instant claims are not patentable in view of the preponderance of evidence and consideration of all the facts which is more convincing than the evidence which has been offered in opposition to it.
Conclusion
No claim is allowed.
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 JIANFENG SONG. Ph.D. whose telephone number is (571)270-1978. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JIANFENG SONG/ Primary Examiner, Art Unit 1613