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
Claims 1-7 are under consideration.
The instant application is identified as divisional (DIV) of Application No. 16/410,599 filed May 13, 2019 (now U.S. Patent No. 11,911,517).
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-7, drawn to a method of preparation comprising the steps of combining, adding, heating, stirring, cooling, combining, cooling and encapsulating in the reply filed on December 18, 2025 is acknowledged.
Upon amendment by Applicant, claims 1-7 are pending.
Claims 1-7 as filed on December 18, 2025 are under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 13, 2024 was considered.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words. It is important that the abstract not exceed 150 words in length since the space provided for the abstract on the computer tape used by the printer is limited. The form and legal phraseology often used in patent claims, such as "means" and "said," should be avoided. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, "The disclosure concerns," "The disclosure defined by this invention," "The disclosure describes," etc.
The abstract of the disclosure is objected to because it is too short and because it is replete with phrases which can be implied, such as, “The present disclosure provides for”. Correction is required. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 112(b)
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 1-7 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 pre-AIA the applicant regards as the invention.
Claim 1(b) recites adding the acetaminophen. There is insufficient antecedent basis for this limitation in the claim. Claims 1-7 are included in this rejection because they depend from claim 1.
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) 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); 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.
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) and (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 required by claim 3, 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.
Conclusion
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