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 .
Information Disclosure Statement
An information disclosure statement has not been received. If the applicant is aware of any prior art or any other co-pending applications not already of record, he/she is reminded of his/her duty under 37 CFR 1.56 to disclose the same.
Response to Amendment
Applicant’s submission filed 06/17/2026 includes changes to the claims, remarks and arguments related to the previous rejection. The above have been entered and considered. Claims 1-2 are currently pending.
Response to Arguments
With regard to the claim objections:
Applicant has amended Claims 1 & 2 to expand and distinctly claim the features cited by acronyms. The claim objection is withdrawn.
With regard to the 112(b) rejection:
Applicant has amended Claim 1 to resolve the clarity of the introductory clause form “selecting” to “comprising”. The 112(b) rejection of the claims is withdrawn.
With regard to the 103 rejection:
Applicant has amended Claim 1 has added a new limitation the requires additional search and consideration.
wherein compound (I) comprises indomethacin and a hard fat;
Applicant’s arguments and/or amendments with regard to Claims 1-2 have been considered in light of the previous references. The arguments and amended claims do not overcome the prior art at the time of the filing of the invention. Upon further consideration, a new ground(s) of rejection is made in view of a new combination of the prior references of Lloyd in view of the new reference of Jiang.
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.
Claims 1 & 2 are rejected under 35 U.S.C. 103 as being unpatentable over Kwong; HPLC Analysis of Indomethacin and Its Impurities in Capsule and Suppository Formulations. Journal of Pharmaceutical Sciences. 1982;71(7):828-830. doi:10.1002/jps.2600710730: “Kwong”) in view of Swift (US 20230090994: “Swift”) and in further view of Jiang (CN 103070860: “Jiang”).
Claim 1. Kwong discloses a high-performance liquid chromatographic (HPLC) method to analyze pharmaceutical composition of a compound (I) or pharmaceutically acceptable salts [Abstract: Indomethacin and its impurities in suppository and capsule formulations were quantitatively determined by HPLC using a re- versed-phase, octadecyl column and a mobile phase of methanol- water-acetonitrile-acetic acid (55:35:101)] thereof, for administration to a body orifice (indomethacin)[Abstract: The latter two impurities were a result of the interaction of indomethacin and 4-chlorobenzoic acid with glycerin used in the suppository base], comprising:
a) preparing standard stock solution by weighing compound of formula (I) [page 829 second col. And 7¶: suppositories (100 mg of I/dose) were weighed and crushed. Five aliquots equivalent to 50 mg were placed in five 50-ml screw-capped culture tubes and treated as described previously] and dissolving in diluent comprising a mixture of acetonitrile and water [Page 829 second col. 4th ¶: of nitrogen at 40 °C, and the residue was reconstituted by addition of 200 μL of acetonitrile-water (7:3, v:v). A 20-μL aliquot was injected onto the LC/MSn system];
b) preparing standard preparation from standard stock solution [page 829 second col. And 7¶: suppositories (100 mg of I/dose) were weighed and crushed. Five aliquots equivalent to 50 mg were placed in five 50-ml screw-capped culture tubes and treated as described previously] by mixing with said diluent [Page 829 second col. 4th ¶: of nitrogen at 40 °C, and the residue was reconstituted by addition of 200 μL of acetonitrile-water (7:3, v:v). A 20-μL aliquot was injected onto the LC/MSn system];
c) preparing a related compound A stock solution by weighing Related compound A and dissolving in said diluent [Page 829 second col. And 7¶: suppositories (100 mg of I/dose) were weighed and crushed. Five aliquots equivalent to 50 mg were placed in five 50-ml screw-capped culture tubes and treated as described previously];
d) preparing Related compound B stock solution by weighing the Related compound B and dissolving in said diluent [Page 829 second col. And 7¶: suppositories (100 mg of I/dose) were weighed and crushed. Five aliquots equivalent to 50 mg were placed in five 50-ml screw-capped culture tubes and treated as described previously];
e) analyzing a sample of pharmaceutical composition of a compound (I) or the pharmaceutically acceptable salts thereof, for administration to a body orifice, wherein a column is provided and the mobile phase is acetic acid and acetonitrile [Page 1 second col. HPLC System-An isocratic HPLC'O equipped with a single piston pump", 204 loop injectorI2, fixed wavelength detectorI3 (254 nm), electronic data system printer/pl~tter*~, and a 5-j~ reversed-phase (C-18) column (4.6 mm X 25 cm)15 were used throughout. The mobile phase consisted of methanol-water-acetonitrile-acetic acid (55:35:10:1) and was pumped at 1 ml/min]; and
f) recording a chromatogram (Figure 1) and measuring response to calculate specified impurity and any individual unspecified impurities identified by Relative Retention Time RRT at about 0.71 and about 1.04 and purity of compound (I) [Table III list of impurities:
4-Chlorobenzoic Acid (II) 0.020 %
5-Methoxy-2-methyl-3-indole-acetic acid (III) 0.070 %
4-Chlorobenzoic acid- a-monoglyceride (IV) 0.390 %
Indomethacin-a-mono- glyceride (V) 0.919 %
Kwong does not explicitly disclose:
1) The column is a Gemini C6-phenyl, (150 mm x 4.6 mm; 3 μm)
2) wherein compound (I) comprises indomethacin and a hard fat
With regard to 1) Swift teaches a chromatographic method of assessing purity of a cytisine, Swift further teaches the diluent is acetonitrile [0042] and in the mobile phase [0049] assessing the purity of a cytisine using a column is a Gemini C6-phenyl, (150 mm x 4.6 mm; 3 μm) [Table 13 line 5 5 Phenyl; 150 × 4.6 mm, 3.0 μm].
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to use Swift’s selection of acetonitrile without methanol in the diluent and mobile phase and column selection of a Gemini C6-phenyl, (150 mm x 4.6 mm; 3 μm) as Kwong’s column analysis because using a consistent organic solvent reduces erroneous peak shifts and selection of the best stationary phase provides good resolution of all impurities and comparable peak shape [Swift 0049 & 0090].
With regard to 2) Jiang teaches a compound (I) comprises indomethacin and a hard fat [0019: in embodiment 51 a saturated fatty acid triglyceride suppository indomethacin 50 mg ibuprofen 125 mg 1325 mg mixing said ingredients, prepared into suppository].
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to use Jiang’s hard fat based indomethacin composition as Kwong’s, as modified, indomethacin composition because a high level of purity can be provided using a triglyceride which does not support contaminating microbial growth [0011: Jiang The indomethacin (purity: 99.54%) used in this invention was produced by Shenyang No. 5 Pharmaceutical Factory].
Claim 2. Kwong discloses a method to analyze purity of ing composition of compound (I) or pharmaceutically acceptable salts [Abstract: Indomethacin and its impurities in suppository and capsule formulations were quantitatively determined by HPLC using a re- versed-phase, octadecyl column and a mobile phase of methanol- water-acetonitrile-acetic acid (55:35:101)] thereof, for administration to a body orifice comprising: analyzing compound (I) using the high-performance liquid chromatographic HPLC conditions (indomethacin)[Abstract: The latter two impurities were a result of the interaction of indomethacin and 4-chlorobenzoic acid with glycerin used in the suppository base], wherein the mobile phase is a mixture of acetic acid and water; acetonitrile [Page 828: second col. First ¶: Methanol, water, and acetonitrile were HPLC quality6, and acetic acid7 and ethers were reagent grade. TLC plates were precoated with silica gel G-25 UV (254) (20 X 20 cm, 0.25 mm). Solvents used for TLC were reagent grade8]; the diluent is a mixture of acetonitrile and water [Page 829 second col. 4th ¶: of nitrogen at 40 °C, and the residue was reconstituted by addition of 200 μL of acetonitrile-water (7:3, v:v). A 20-μL aliquot was injected onto the LC/MS system]; and the column to determine presence of Related compound A and Related compound B [Page 828 second Col. Second ¶: HPLC System-An isocratic HPLC'O equipped with a single piston pump", 204 loop injectorI2, fixed wavelength detectorI3 (254 nm), electronic data system printer/plotter*~, and a 5-j~ reversed-phase (C-18) column (4.6 mm X 25 cm)15 were used throughout. The mobile phase consisted of methanol-water-acetonitrile-acetic acid (55:35:10:1) and was pumped at 1 ml/min], any individual unspecified impurities identified by Relative Retention Time RRT at about 0.71 and about 1.04 and purity of compound (I), and quantifying Related compound A and Related compound B.
Table III list of impurities by % of compound with impurities between .71 % and 1.04 %:
4-Chlorobenzoic Acid (II) 0.020 %
5-Methoxy-2-methyl-3-indole-acetic acid (III) 0.070 %
4-Chlorobenzoic acid- a-monoglyceride (IV) 0.390 %
Indomethacin-a-mono- glyceride (V) 0.919 %
Kwong does not explicitly disclose:
1) The dilution medium is acetonitrile.
2) The column is a Gemini C6-phenyl, (150 mm x 4.6 mm; 3 μm).
With regard to 1) Swift teaches a chromatographic method of assessing purity of a cytisine, Swift further teaches the diluent is acetonitrile [0042] and in the mobile phase [0049] assessing the purity of a cytisine using a column is a Gemini C6-phenyl, (150 mm x 4.6 mm; 3 μm) [Table 13 line 5 5 Phenyl; 150 × 4.6 mm, 3.0 μm].
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to use Swift’s selection of acetonitrile without methanol in the diluent and mobile phase and column selection of a Gemini C6-phenyl, (150 mm x 4.6 mm; 3 μm) as Kwong’s column analysis because using a consistent organic solvent reduces erroneous peak shifts and selection of the best stationary phase provides good resolution of all impurities and comparable peak shape [Swift 0049 & 0090].
With regard to 2) Jiang teaches a compound (I) comprises indomethacin and a hard fat [0019: in embodiment 51 a saturated fatty acid triglyceride suppository indomethacin 50 mg ibuprofen 125 mg 1325 mg mixing said ingredients, prepared into suppository].
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to use Jiang’s hard fat based indomethacin composition as Kwong’s, as modified, indomethacin composition because a high level of purity can be provided using a triglyceride which does not support contaminating microbial growth [0011: Jiang The indomethacin (purity: 99.54%) used in this invention was produced by Shenyang No. 5 Pharmaceutical Factory].
Conclusion
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 Monica S Young whose telephone number is (303)297-4785. The examiner can normally be reached M-F 08:30-05:30 MST. 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.
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/MONICA S YOUNG/Examiner, Art Unit 2855
/PETER J MACCHIAROLO/Supervisory Patent Examiner, Art Unit 2855
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