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 .
DETAILED ACTION
Applicant’s Request for Reconsideration dated June 9, 2026 is acknowledged.
Claims 1-7 are pending.
Claim 8 is cancelled.
Claims 1 and 3 are currently amended.
Claims 1-7 as filed on June 9, 2026 are under consideration.
This action is made FINAL.
Withdrawn Objections / Rejections
In view of the new abstract, all previous objections to the specification are withdrawn.
In view of the amendment of the claims, all previous claim rejections under 35 USC 112(b) are withdrawn.
Applicant’s arguments have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Specification
The disclosure is objected to because of the following informalities: the first sentence of the abstract is incomplete. Appropriate correction is required.
Maintained Grounds of Rejection / New Grounds of Rejection Necessitated by Amendment
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.
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 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Rogers et al (WO 85/03439, published August 15, 1985, of record) in view of Tran et al. (WO 2018/183082, published October 4, 2018, IDS reference filed September 13, 2024); Fu et al. (CN 103463087 A, published July 29, 2015, as evidenced by the Google translation, of record); Modi et al. (US 2011/0020440, published January 27, 2011, IDS reference filed September 13, 2024); and Ahumada et al. “Solution thermodynamics of acetaminophen in some PEG 400 + water mixtures,” Fluid Phase Equilibria 332:120-127, 2012, of record.
Rogers teaches soft gelatin capsules containing an effective dosage of acetaminophen; the acetaminophen is in the form of particles, however, minor amounts of acetaminophen are dissolved (title; abstract; claims, in particular 2, 24; page 7, lines 3-10). Acetaminophen is an analgesic (page 1, lines 8-11). The effective dosage of acetaminophen ranges from 325 to 650 mg (page 5, lines 29-30), as required by instant claim 7. 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). "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05. Rogers further teaches a method comprising (claim 28):
preparing fill material comprising acetaminophen and polyethylene glycols inclusive of those having an average MW of about 400 to 1000; and
encapsulating said fill material in a gelatin shell.
The shell is formulated according to conventional techniques and may comprise plasticizers such as glycerin or sorbitol and may comprise water (page 4, lines 7-13).
Rogers does not specifically teach (a) combining polyethylene glycol and povidone to provide a mixture; (b) adding acetaminophen; (c) adding dextromethorphan HBr, either phenylephrine HCl or pseudoephedrine, and polyethylene glycol; (d) heating and stirring; (e) cooling to provide a suspension; (f) combining sorbitol-sorbitan solution, glycerin, water, one or more colorants and gelatin to provide an outer shell mixture; (g) cooling the outer shell mixture; and (h) encapsulating the suspension with the outer shell mixture as required by claim 1.
Rogers does not teach the one or more (optional) further active pharmaceutical ingredients is selected from the group consisting of doxylamine succinate, chlorpheniramine maleate, and guaifenesin as required by claim 2.
Rogers does not teach steps (a), (b), (c) or (d) are performed at a temperature of between 40°C and 45°C as required by claim 3.
Rogers does not teach cooling mixture (d) to a temperature of between 28°C and 32°C as required by claim 4.
Rogers does not teach step (f) is performed at a temperature between about 80°C and about 95°C as required by claim 5.
Rogers does not teach the outer shell mixture is cooled to a temperature of between about 55°C and about 65°C as required by claim 6.
Rogers does not teach between about 5 mg and about 20 mg dextromethorphan HBr and between about 2.5 mg and about 10 mg phenylephrine HCl or a therapeutically equivalent amount of pseudoephedrine as required by claim 7.
These deficiencies are made up for in the teachings of Tran, Fu, Modi and Ahumada.
Tran teaches capsules comprising one or more of a decongestant, an expectorant, an antitussive, an analgesic such as acetaminophen and/or an antihistamine (title; abstract; claims; Figures; page 6, lines 4-7). The capsules comprise two or more of acetaminophen, guaifenesin (expectorant), phenylephrine (decongestant), dextromethorphan (antitussive), diphenhydramine (antihistamine) or pseudoephedrine (decongestant), for example, the capsules comprise about 200 mg guaifenesin, about 5.25 mg phenylephrine HCl and about 10.526 mg dextromethorphan HBr (95%) (claims 1, 14), as required by instant claims 2, 7. Combination medicines are sought for their convenience (page 1, lines 10-19). Tran further teaches a method of for fill preparation as exemplified in Figure 2 (also, page 7, lines 5-25):
PNG
media_image1.png
718
672
media_image1.png
Greyscale
In some embodiments the temperature during the addition of dextromethorphan is up to 55 ºC, the temperature during the addition of phenylephrine is below 35 ºC, and final fill preparation is cooled to ambient temperature (page 7, lines 5-25). Tran further teaches a method of for capsule shell preparation as exemplified in Figure 1:
PNG
media_image2.png
610
664
media_image2.png
Greyscale
, as required by instant claims 5, 6. Tran further teaches a method for encapsulation in Figure 3 wherein the fill preparation is combined with the capsule shell preparation. Tran further teaches acetaminophen tends to recrystallize in solution (page 1, lines 16-17).
Fu teaches a preparation method of night cold-treating soft capsules wherein the excipients of the gelatin solution for the capsule shells are first added to a tank heated to 40 to 80 ºC and the gelatin is subsequently added to the tank and heated to 60 to 80 ºC (title; abstract; claims, in particular 1; Examples), as required by instant claim 5. The fill solution is prepared by a process wherein polyethylene glycol and povidone are mixed, acetaminophen is added and heated to 50 to 90 ºC, the solution is cooled to below 40 ºC, and dextromethorphan HBr and doxylamine succinate are added and maintained at a temperature below 40 ºC (title; abstract; claims, in particular 1; Examples), as required by instant claims 2-4.
Modi teaches soft gelatin capsules containing at least one sparingly soluble active drug such as acetaminophen and a solvent system comprising inter alia a solvent such as polyethylene glycol and a crystal growth inhibitor such as povidone (title; abstract; claims, in particular 2-4, 11, 13, 16, 18; paragraphs [0033], [0038], [0043]; Examples 7-14). The capsules may further comprise freely soluble drugs selected from antihistamines inclusive of doxylamine succinate, antitussives inclusive of dextromethorphan HBr, and decongestants inclusive of phenylephrine HCl (claims 4, 11).
Ahumada teaches the solubility of acetaminophen in PEG 400 is relatively high and illustrates the effect of temperature on the solubility; an increase in temperature increases solubility (title; abstract; conclusions; Tables 1 and 2 when w1 = 1).
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 method of Rogers for preparing the fill material for soft gelatin capsules comprising acetaminophen particles to further comprise subsequent steps of adding and mixing one or more of dextromethorphan HBr, phenylephrine HCl and guaifenesin as illustrated by Tran in Figure 2 because combination medicines are sought for their convenience.
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 method of Rogers in view of Tran for preparing the combination fill material to further comprise a step wherein povidone is pre-mixed with polyethylene glycols as illustrated in Figure 2 of Tran because Tran teaches acetaminophen tends to recrystallize and it is known from Modi that povidone acts as a crystal growth inhibitor. One would be motivated to do so inhibit crystal growth of the minor amounts of acetaminophen Rogers teaches to dissolve.
Regarding the order of mixing of steps (a) – (c) as required by claim 1, selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. See MPEP 2144.04 IV (C).
Regarding steps (d) and (e), 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 method of Rogers in view of Tran and Modi to further comprise mixing as taught by Tran and by Fu under heating and maintaining at a temperature below 40 ºC (cooling) as taught by Fu in order to ensure the combination fill material is completely mixed and in order to keep the combination fill material in a state ready for encapsulation. Regarding the step of heating, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to minimize / optimize the heating temperature in order to not dissolve the acetaminophen during processing because it is known from Ahumada that the solubility of acetaminophen increases with temperature. It is prima facie obvious to optimize such result-effective variables within prior art conditions or through routine experimentation. See MPEP 2144.05.
Regarding steps (f) and (g), 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 formulation of the shell of Rogers for the combination fill material of Rogers in view of Tran, Modi, Fu and Ahumada to comprise steps as illustrated in Figure 1 of Tran including keeping the shell material at a temperature at 55 to 65 ºC (cooling) because such method is suitable for encapsulating acetaminophen. There would be a reasonable expectation of success because Rogers embraces shell formulations according to conventional techniques.
Regarding step (h), the combined teachings of Rogers in view of Tran, Modi and Fu render obvious encapsulation as claimed to provide a soft gel capsule as claimed.
Regarding the temperature of between 40°C and 45°C of steps (a) – (d) as alternatively required by claim 3 as currently amended, the combined teachings of the prior art render obvious the minimization / optimization of the temperature in order to not dissolve the acetaminophen during processing because it is known from Ahumada that the solubility of acetaminophen increases with temperature. Therefore, it would have been obvious to manufacture the combination fill material of Rogers in view of Tran, Modi, Fu and Ahumada at temperatures below the 70 ºC illustrated by Tran in Figure 2 and below the 50 to 90 ºC as taught by Fu. See MPEP 2144.05.
Regarding the temperature of between about 80°C and about 95°C of step (f) as required by claim 5, the combined teachings of Rogers in view of Tran render temperatures of the gel melter tank of 60 to 80 ºC and in view of Fu it would have been obvious to operate at temperatures of 60 to 80 ºC even after the gelatin is subsequently added. See MPEP 2144.05.
Regarding claim 7, the combined teachings of the prior art render obvious soft gelatin capsules comprising from 325 to 650 mg acetaminophen and 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 method of Rogers in view of Tran, Fu, Modi and Ahumada to include the acetaminophen within this amount in order to produce a single capsule. It would have been obvious to include the dextromethorphan HBr in the single capsule in an amount of about 10.526 mg as taught by Tran because this is a therapeutically effective amount and it would have been obvious to modify the method of the combined teachings of the prior art to include the dextromethorphan HBr in this amount. It would have been obvious to include the phenylephrine HCl in the single capsule in an amount of about 5.25 mg as taught by Tran because this is a therapeutically effective amount and it would have been obvious to modify the method of the combined teachings of the prior art to include the phenylephrine HCl in this amount.
Response to Arguments: Claim Rejections - 35 USC § 103
Applicant’s arguments have been fully considered but they are not persuasive.
Applicant argues the rejection is hindsight because the technical goals of the secondary references differ from that of the base reference.
This is unpersuasive because the prevailing legal standard is not the problem – solution approach but rather an assessment, based on evidenced facts, of what would have been obvious to one of ordinary skill in the art. In order to traverse a rejection, Applicant must include a reasoned statement explaining why the Applicant believes the Office has erred substantively as to the factual findings. See MPEP 2141 IV and 37 CFR 1.111(b).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant argues the technical challenge disclosed in the instant specification (e.g., paragraph [0080]) is to manage physical stability of particles. Applicant argues a person of ordinary skill in the art would not combine references drawn to solutions with Rogers.
This is unpersuasive because claim 1, step (e) does not in fact recite a limitation drawn to a stable suspension as stated at page 5 of the Remarks. Nor is paragraph [0080], which is drawn to some embodiments comprising doxylamine succinate, drawn to stability. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Nonetheless, Rogers expressly discloses stable products (e.g., page 6, lines 6-12), suggesting the alleged technical problem addressed in the instant specification has long been solved.
Applicant’s argument that one would not combine references drawn to solutions with the suspension of Rogers is unpersuasive because it is understood from the cited references that acetaminophen may be administered in numerous ways (e.g., Rogers, “Description of the Prior Art”). And the references are all drawn to acetaminophen. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
While the acetaminophen of Tran may be dissolved, the so-called technical problem addressed by Tran is to provide “desirable combinations of active ingredients” (e.g., page 1, “Summary of Invention”). In view of Tran, one of skill in the art would have found it obvious and would have been motivated to modify the dosages of Rogers in order to provide “desirable combinations of active ingredients” and would have been motivated to modify the method of Rogers with suitable method steps in order to achieve this objective. And in view of Modi, one of skill in the art would have known that povidone acts as a crystal growth inhibitor for acetaminophen as set forth in the rejection and would have been motivated to include povidone in order to mitigate recrystallization of the minor amounts of acetaminophen that may be dissolved in the dosages of Rogers.
Applicant argues the cited references fail to suggest the critical split-addition of PEG.
This is unpersuasive because there is no evidence of record demonstrating the split-addition of PEG to be critical. To the contrary, the instant specification at most suggests the split or “reserved portion” is used to aid in the flow of the APIs (e.g., Example 1 at paragraphs [0198]-[0200]). See MPEP 2145 I, Argument does not replace evidence where evidence is necessary.
Applicant argues a person of ordinary skill in the art would be motivated to use the high heat of the secondary references.
This is unpersuasive because the rejection addresses this specific concern in articulating a rationale to avoid high heat in order to “not dissolve the acetaminophen during processing”.
Applicant argues the processing temperature of 40 to 45 ºC defines a critical, non-linear thermodynamic and physical window.
This is unpersuasive because there is no evidence of record substantiating such an allegation. See MPEP 2145 I. The argument that the lower boundary is determined by viscosity is unpersuasive because PEG comes in various grades with various viscosities, as does povidone. Furthermore, Rogers is in possession of a PEG vehicle for acetaminophen particles and expressly addresses manufacturing needs (e.g., page 6). As such, Rogers evidences manufacturing adjustments are within the skill of the ordinary artisan and fall within the scope of routine optimization. The argument that the upper boundary is determined by solubility is acknowledged, however, the rejection addresses this specific concern in articulating a rationale to operate at temperatures which minimize dissolution.
Applicant argues the motivation to combine povidone is based on a flawed premise which requires acetaminophen to be dissolved.
This is unpersuasive because Rogers expressly teaches minor amounts of acetaminophen are dissolved. And it would be undesirable to have said dissolved acetaminophen recrystallize into large, irregular needle-like crystals as described at page 8 of the Remarks. Modi evidences the inclusion of povidone solves this problem.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kasai et al. (JP S 6092214 A, as evidenced by the Google translation) teaches soft capsules comprising a dispersion of acetaminophen in macrogol and further comprising, e.g., an antitussive, expectorant, antihistamine, etc. (title; abstract; claims).
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 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 ALISSA PROSSER whose telephone number is (571)272-5164. The examiner can normally be reached M - Th, 10 am - 6 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, DAVID BLANCHARD can be reached on (571)272-0827. 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.
/ALISSA PROSSER/
Examiner, Art Unit 1619
/BENNETT M CELSA/Primary Examiner, Art Unit 1600
Prosecution Insights