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 .
Applicant’s election without traverse of Group I, claims 1-6, 9, 10, 12, 15, and 17-26, in the reply filed on 06/08/2026 is acknowledged.
Applicant’s election of the following species are acknowledged:
Excipient: Applicant elects a combination a combination of a filler, disintegrant, and a lubricant;
Filler: Applicant elects a combination of microcrystalline cellulose, erythritol, xylan, and corn starch.
Disintegrant: Applicant elects a combination of soybean polysaccharide, glucuronic acid, and alginic acid;
Lubricant: Applicant elects glyceryl distearate.
Claims 5, 10, 15, and 20-26, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/08/2026.
Claim Status
Claims 1-6, 9, 10, 12, 15, and 17-26, are pending.
Claims 5, 10, 15, and 20-26, are withdrawn.
Claim Rejections - 35 USC § 112(b) or pre-AIA 2nd ¶
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6, 12, 17, and 18, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 6 recites the limitation "the alginic acid" in line 2. There is insufficient antecedent basis for this limitation in the claim. The claim depends from claim 1, where there appears to be no recitation of alginic acid.
Claims 6, 12, and 17, recite a ratio of components, wherein the ratio ranges are surrounded by parenthesis. Accordingly, it is unclear if the parenthetical ranges are required, or simply an example or an optional limitation. For purposes of examination, the claims will be interpreted without the parenthesis (e.g., 1-5:1:1-3).
Claim 18 recites components in terms of parts by weight, and it is unclear if the parts by weight are to total up to 100 parts by weight, or something else, where the claim allows for a total parts by weight as high as 118, not including the lubricant as elected by Applicants. For purposes of examination, the examiner is interpreting any amounts that fall within the recited ranges, as reading the claimed ranges.
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, 4, 6, 9, 12, 17, and 19, are rejected under 35 U.S.C. 103 as being unpatentable over Lindenblatt et al (US 20150231101 A1, hereinafter “Lindenblatt”), in view of Huang et al (Chinese Pharmaceutical Journal, vol 40, no 19, 31, 2005, pp. 1441-1444, cited on IDS dated 05/01/2024, hereinafter “Huang”), Hemmingsen et al (US 20100239667 A1, hereinafter “Hemmingsen”), and Nihira et al (US 20150238607 A1, hereinafter “Nihira”), as evidenced by Guide Chem (Ghatti Gum, retrieved 2026).
Lindenblatt teaches solid pharmaceutical preparations comprising levothyroxine sodium (abs). The preparations can be in the form of microtablets (¶¶ 27, 28, 40). The preparation further comprises fillers including microcrystalline cellulose, sugar alcohols, maize starch (i.e., corn starch), etc. (¶ 23). In embodiments, the preparation may contain disintegrating agents in order to shorten the disintegration time of the tablet, enabling the active to be released rapidly (¶¶ 30-33, claim 8). When in tablet form, the preparation also comprises lubricants, including glyceryl distearate, in order to reduce sliding friction of the tableting material and ram in the mold during the tableting operation and to prevent sticking to the rams (¶ 37). The levothyroxine sodium is present in micronized form with a particle size from 5-25 microns (¶ 14). In embodiments, the disintegrating agent may be included at 0.01 to 20 wt% (¶ 33). In embodiments, levothyroxine sodium is included at 0.075 wt%, 0.3 wt%, 0.105 wt%, and 0.025 wt% (ex 1-12).
Lindenblatt does not appear to teach the particle diameter instantly claimed, the total tablet weight as instantly claimed, nor the excipients erythritol, xylan, soybean polysaccharide, glucuronic acid, and alginic acid.
Huang teaches minitablets were known to disperse evenly in the gastrointestinal tract, minimizing the impact of gastric emptying rate on drug transportation and absorption, thus resulting in minimal individual variability (pg 1441 1st col 1st ¶). Minitablets have a dimeter ranging from 2-3 mm (pg 1441 1st col 1st ¶). Particle sizes of the tableting mixtures were investigated and it was found that the tablet properties of the resulting tablets varied with the particle size of the mixture, where the smaller the particle size, the better the tablet properties (pg 1442 2nd col 1st ¶). In embodiments, microtablets were known to be formulated with a diameter of 2 mm and a tablet weight of 7.5 mg (2.1). Compared to the tablet does of 300 mg, the 7.5 mg tablet showed higher bioavailability (2.1).
Huang does not teach the excipients erythritol, xylan, soybean polysaccharide, glucuronic acid, and alginic acid.
Hemmingsen teaches pharmaceutical compositions that may be in the form of minitablets, and can comprise levothyroxine sodium as the active agent (abs, ¶¶ 86, 123, 139). The composition may also contain other excipients to improve the technical properties of the composition so that it may be easier to produce or in order to improve the properties of the composition such as release rate of the active substance, stability, etc. (¶ 178). Suitable excipients include saccharides, alginic acid, microcrystalline cellulose, starches including maize starch, ghatti gum, lubricants, disintegrants, etc. (¶ 180). As evidenced by Guide Chem, ghatti gum comprises glucuronic acid and acts as a disintegrant in tablet formulations (Question and Answer). Saccharides include erythritol, xylan, etc. (¶ 195).
Hemmingsen does not appear to teach soybean polysaccharide.
Nihira teaches soybean polysaccharide was a known disintegrant suitable for pharmaceutical formulations in the form of a tablet (¶¶ 433, 435).
Regarding the minitablet diameter of claim 1, it would have been obvious to formulate the microtablets of Lindenblatt with a tablet diameter of 2-3 mm, where minitablets of these sizes were known to minimize the impact of emptying rate on drug transportation and absorption, thus resulting in minimal individual variability, as taught by Huang.
Regarding the tablet weight, it would have been obvious to formulate the minitablets made obvious above with known total tablet weights suitable for minitablets, including 7.5 mg, where these weights were known to improve bioavailability compared to larger tablet weights, as taught by Huang.
Regarding the active and excipients, it would have been obvious to formulate the minitablet made obvious above comprising levothyroxine sodium and excipients, as taught by Lindenblatt.
Regarding Applicants’ elected excipients, it would have been obvious for the skilled artisan to formulate the minitablet with known excipients suitable for levothyroxine sodium microtablets, including microcrystalline cellulose (filler), sugar alcohols (filler), corn starch (filler), glyceryl distearate (lubricant), as well as disintegrants, where Lindenblatt teaches combinations of excipients are suitable.
It would have been obvious to further include other known excipients that were known to be suitable for minitablets comprising levothyroxine sodium, including alginic acid (disintegrant), ghatti gum (disintegrant, comprises glucuronic acid), and saccharides including erythritol (filler) and xylan (filler), in order to formulate compositions that are easier to produce, improve the technical properties of the composition, optimize release rate, etc., as taught by Hemmingsen, and where Lindenblatt teaches fillers and disintegrating agents are included.
Further, where Lindenblatt teaches the inclusion of disintegrating agents, it would have been obvious for the skilled artisan to further include other known disintegrating agents suitable for pharmaceutical tablet formulations, such as soybean polysaccharide, as taught by Nihira, in order to achieve desired disintegration and release rates of the minitablet made obvious above.
The skilled artisan would have had a reasonable expectation of success in combining the minitablet made obvious above with the excipients made obvious above, where Lindenblatt, Hemmingsen, and Nihira are all directed to pharmaceutical tablet formulations comprising an active agent.
Regarding claim 2, it would have been obvious to formulate the minitablet made obvious above with a diameter of 2-3 mm and a tablet weight of 7.5 mg, for the same reasons discussed above by Huang.
Regarding claims 3 and 4, where Lindenblatt teaches that the active agent is micronized with a particle size ranging from 5-25 microns, in the case of microtablets, and where Huang teaches that smaller particle sizes of tableting mixtures are better for tablet properties, it would have been obvious for the skilled artisan to formulae the active ingredient with a particle size of 5-25 microns. While the D90 of the particle sizes is not specifically taught, where the particle sizes are taught to range from 5-25 microns, it appears the D90 would fall within the claimed range of less than or equal to 250 microns.
Purely arguendo, if not, it would have been obvious for the skilled artisan to routinely optimize the particle sizes, including the D90, where Huang teaches that the smaller the particle size, the better for minitablets. Further, the skilled artisan would reasonably recognize that having a tighter particle dispersion of the components would be optimal for formulating tablets with increased drug and tablet uniformity, weight variability, more consistent minitablet properties, etc.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where 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. See MPEP 2144.05(II)(A).
Regarding the ratio of claims 6 and 9, where the minitablet made obvious above comprises a mixture of soybean polysaccharide, ghatti gum (contains glucuronic acid), and alginic acid, it would have been well within the relative skills of the skilled artisan to routinely adjust the mixing ratios of the individual components of the disintegrant mixture, in order to achieve desired and optimal disintegration properties, disintegration time, release rate, etc., depending on desired treatments, route of administration, etc. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where 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. See MPEP 2144.05(II)(A).
Regarding claim 12, where the minitablet made obvious above comprises a mixture of microcrystalline cellulose, erythritol, xylan, and corn starch, it would have been well within the relative skills of the skilled artisan to routinely adjust the mixing ratios of the individual components of the filler mixture, in order to achieve desired and optimal tablet properties, where the skilled artisan would recognize that adjusting the ratios would result in tablets having varying hardness, dissolution, release rates, flowability, etc., depending on the desired treatments, route of administration, etc. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where 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. See MPEP 2144.05(II)(A).
Regarding claim 17, where Lindenblatt teaches the amount of filler and disintegrants can vary, it would be reasonably expected that the skilled artisan would recognize that more disintegrant compared to filler would result in faster disintegration, and vice versa. Accordingly, it would have been well within the relative skills of the skilled artisan to routinely adjust the ratio of filler to disintegrant, where doing so would reasonably be expected to adjust the disintegration rate of the tablets, in order to optimize the tablets for desired treatments, mode of administration, etc. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where 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. See MPEP 2144.05(II)(A).
Regarding claim 19, the minitablet made obvious above comprises levothyroxine sodium, thereby meeting the claimed limitation.
Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Lindenblatt et al (US 20150231101 A1, hereinafter “Lindenblatt”), Huang et al (Chinese Pharmaceutical Journal, vol 40, no 19, 31, 2005, pp. 1441-1444, cited on IDS dated 05/01/2024, hereinafter “Huang”), Hemmingsen et al (US 20100239667 A1, hereinafter “Hemmingsen”), and Nihira et al (US 20150238607 A1, hereinafter “Nihira”), and further in view of Reddy et al (US 20170119678 A1, hereinafter “Reddy”).
The references are discussed above, and purely arguendo, if somehow the particle size D90 of claims 3 and 4 are not obvious, the following applies.
Reddy teaches it was known to formulate pharmaceutical mini tablets with a particle size d90 ranging from 1 to 10 microns (¶ 16).
Regarding claims 3 and 4, where Huang teaches smaller particle sizes are better for minitablets, it would have been obvious for the skilled artisan to formulate the particle sizes with a known d90 suitable for pharmaceutical minitablets, such as from 1 to 10 microns, as taught by Reddy, where the skilled artisan would reasonably recognize that a smaller d90 would result in increased drug and tablet uniformity, weight variability, more consistent minitablet properties, etc.
Claims 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Lindenblatt et al (US 20150231101 A1, hereinafter “Lindenblatt”), Huang et al (Chinese Pharmaceutical Journal, vol 40, no 19, 31, 2005, pp. 1441-1444, cited on IDS dated 05/01/2024, hereinafter “Huang”), Hemmingsen et al (US 20100239667 A1, hereinafter “Hemmingsen”), and Nihira et al (US 20150238607 A1, hereinafter “Nihira”), and further in view of Hidalgo et al (WO 2011098194 A2, hereinafter “Hidalgo”).
The references are discussed above but do not appear to specifically teach the parts by weight of the filler of claim 18. Further, claim 17 is discussed above, and purely arguendo, if somehow it would not have been obvious to adjust the amount of filler based on the teachings of Lindenblatt, the following applies.
Hidalgo teaches it was known to formulate pharmaceutical mini tablets comprising microcrystalline cellulose (filler), a disintegrant, a lubricant, etc., where it was known to include microcrystalline cellulose in an amount ranging from 2 to 50 wt% of the total mini tablet (abs, pg 6 ln 4-7, claims 3, 6). The disintegrant can be included up to 10 wt% (claim 5).
Regarding claim 17, it would have been obvious to modify the minitablet made obvious above by adjusting the amount of filler to other amounts known to be suitable for pharmaceutical minitablets, such as 2 to 50 wt%, as taught by Hidalgo, and include disintegrants in amount ranging from 0.01 to 20 wt%, as taught by Lindenblatt. From there, the skilled artisan can reasonably adjust the amounts of each component within the known ranges, thereby appearing to overlap the instantly claimed mass ratios. Further, as discussed above, it would have been well within the relative skills of the skilled artisan to routinely adjust the ratio of filler to disintegrant, where doing so would reasonably be expected to adjust the disintegration rate of the tablets, in order to optimize the tablets for desired treatments, disintegration times, mode of administration, etc. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where 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. See MPEP 2144.05(II)(A).
Regarding the active ingredient of claim 18, it would have been obvious to formulate the minitablet with 0.075 wt%, 0.3 wt%, or 0.105 wt%, from the working examples of Lindenblatt.
Regarding the amount of filler of claim 18, it would have been obvious to modify the minitablet made obvious above by adjusting the amount of filler to other amounts known to be suitable for pharmaceutical minitablets, such as 2 to 50 wt%, as taught by Hidalgo, thereby appearing to overlap the instantly claimed range of 20 to 30 parts filler. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding the amount of disintegrant of claim 18, it would have been obvious to formulate the minitablet with disintegrant in an amount ranging from 0.01 to 20 wt%, as taught by Lindenblatt, depending on desired disintegration times, release rates, etc.
Further, it would have been well within the relative skills of the skilled artisan to have routinely optimized the amount of active ingredient, filler, and disintegrant, depending on desired treatments, disintegration time, tablet properties, flowability, etc. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where 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. See MPEP 2144.05(II)(A).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSHUA A ATKINSON whose telephone number is (571)270-0877. The examiner can normally be reached M-F: 9:00 AM - 5:00 PM + Flex.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at 571-272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOSHUA A ATKINSON/
Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
Prosecution Insights