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 . The filing date is 7/7/2022.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 15, 2026 has been entered.
Status of the Claims
Claims 8 and 10-14 are pending in this application and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on Jan 15 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicant's arguments and amendment to claim 8, filed January 15, 2026, with regard to the rejection of claims 8 and 10-14 as being obvious over Zhang 2006, in view of USP Indomethacin Suppositories 2019 and in further view of the 858 patent and/or the 630 patent have been fully considered, necessitating the new rejections below.. Applicant has amended claim 8 to recite the limitation of a “a Hard Fat base having a hydroxyl value not greater than 10 mg KOH/g,” thus necessitating the below new rejection. The previous obvious rejections of claims 8, 11 and 14 (over Zhang in view of USP 2019); claims 8 and 11-14 (over Zhang et al. in view of USP 2019, in further view of ‘858 patent; and claims 8, 10-11 and 14 (over Zhang et al. in view of USP 2019, in further view of (‘858 patent) and (‘630 patent), are withdrawn.
New Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 8, 11 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. “Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana,” Acta Pharmacol. Sin. 2006 Aug; 27 (8): 1097–1102) in view of USP Indomethacin Suppositories 2019 and Google English Translation JP2005314241 A (JP 241), published Nov 10 2005, accessed April 17 2026.
Zhang and USP Indomethacin Suppositories were previously cited by the Examiner in the non-final office action. English Translation JP 241 is listed on the PTO-892 form.
Examined claim 8 is directed to a storage stable pharmaceutical composition for administration to a body orifice, comprising a compound (I) (indomethacin), defined by the chemical structure:
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or a pharmaceutically acceptable salt thereof having a purity of about 99. 5% or more and less than about 0.3% each individual impurity identified by relative retention time (RRT) at 0.71 and 1.04 as measured by high performance liquid chromatography (HPLC),
a Hard Fat base having a hydroxyl value not greater than 10 mg KOH/g,
wherein the composition retains at least 99.5% of the compound (I)(% purity) after storage for 3 months at 30±2°C temperature and 65% relative humidity (% RH).
Regarding claim 8 and the limitations of indomethacin and purity of about 99.5% or more and less than 0.3 % impurity, Zhang 2006 discloses its indomethacin was 99.5% pure and purchased from Dongyu Pharmaceutical (Shenyang China). See page 1098, column 1, reproduced below.
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Regarding claim 8 and the limitation of a pharmaceutical composition for administration to a body orifice, Zhang 2006 teaches that indomethacin is a NSAID agent with anti-pyretic and analgesic properties “extensively used because of its pharmaceutical properties.” See page 1097, column 1.
Regarding claim 8 and a pharmaceutical composition comprising indomethacin of a purity of about 99.5% or more, as noted above, Zhang 2006 discloses its indomethacin was 99.5% pure and purchased from Dongyu Pharmaceutical (Shenyang China). See page 1098, column 1, reproduced below.
Regarding claim 8 and the limitation of “wherein the composition retains at least 99.5% of the compound (I)(% purity) after storage for 3 months at 30±2°C temperature and 65% relative humidity (% RH),” it is pointed out that limitation is directed to a functionally descriptive “storage” property of the pharmaceutical composition defined by the preamble physical description of a storage stable pharm. composition for administration to a body orifice comprising indomethacin with the claimed purity of 99.5% and less than about 0.3% of each individual impurity identified by the claimed RRT measurements by HPLC. Because the physically described limitations of the composition of claim 8 (a storage stable pharm. composition comprising indomethacin with the claimed purity and impurity limitations), the functionally descriptive property of the composition’s purity under the claimed storage conditions would necessarily be present in the prior art teaching claimed composition.
While Zhang 2006 teaches the suitability of indomethacin for use in pharmaceutical compositions, it does not teach the limitation where the pharmaceutical composition suitable for administration to body orifice, for example a suppository, where purity would be measure by HP Liquid Chromatography (HPLC).
Nor does Zhang 2006 teach the limitation of a Hard Fat base having a hydroxyl value not greater than 10 mg KOH/g.
USP Indomethacin Suppositories 2019 teaches the claimed indomethacin as suppositories which are known to be administered to a body orifice. See page 1. One of ordinary skill in the art would formulate such suppositories, based off the teachings of Zhang 2006 which teaches bulk indomethacin with a known pharmaceutical utility that is 99.5% pure and USP Indomethacin Suppositories 2019 teach pharmaceutical compositions suitable for administration to a body orifice.
Further, USP Indomethacin Suppositories 2019 teaches of evaluating the Indomethacin suppositories by liquid chromatography (LC) assay procedures, as per USP Chapter <621> Chromatography. See page 2, column 1 reproduced below.
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Regarding claim 8 and the limitation of a Hard Fat base having a hydroxyl value not greater than 10 mg KOH/g, it is noted that a problem to be solved in the field of the art of suppositories, is to manufacture a hard fat suppository, where quenching and solidification can result in cracking and fragmentation of the suppository, and where slow cooling, while avoiding cracking, may not be efficient for mass production by an automatic filling machine. See Abstract page 1 of English Translation of JP241.
English Translation of JP241 teaches a hard fat (as carrier, with a hydroxyl value ≤10) drug suppository, results in the suppression of cracks in the suppository being suppressed. See bullet point (1) on page 2.1
In other words, English Translation of JP241 teaches the solution to avoid the cracks in a suppository during manufacture, is to use a hard fat having ≤10 hydroxy value to allow for quenching and solidification using an automatic filing molding machine to control the occurrence of cracks and fragments and the suppository is suitable for mass production. See Abstract page 1.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the primary reference Zhang 2006 with the claimed indomethacin purity to modify it with the secondary USP Indomethacin Suppositories reference, with further guidance from JP 241 to use the hard fat with the hydroxy value claimed in order to arrive at the claimed indomethacin suppository.
The PHOSITA would have had a reasonable expectation of success because a PHOSITA would have the rationale to combine the known prior art elements of pure indomethacin and indomethacin suppositories so as to predictably arrive at the claimed invention.
Claim 11 recites the same 99.5% or more purity limitation of indomethacin, as well as the known method of HPLC to determine purity. As noted above, the as Zhang 2005 and USP Indomethacin Suppositories teach the claimed pharmaceutical composition of claim 1 with the same purity limitation of 99.5% or more of composition I (indomethacin), one of ordinary skill in the art would routinely optimize formulating the claimed indomethacin pharmaceutical composition with known 99.5% or more purity so as to arrive at the functional descriptive limitation of storage conditions of claims 9 and 11, as well as rely upon the known method of determining purity via HPLC as per USP Indomethacin Suppositories.
Regarding claim 14 and the limitation of the composition to be delivered by through a rectal administration route, such as a suppository, USP Indomethacin Suppositories 2019 teaches indomethacin suppositories known to be administered via rectal route. See page 1.
Claims 8 and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. “Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana,” Acta Pharmacol. Sin. 2006 Aug; 27 (8): 1097–1102) in view of USP Indomethacin Suppositories 2019 and Google English Translation JP2005314241 A (JP 241), published Nov 10 2005, accessed April 17 2026, in further view of U.S. Patent 4,681,858 (‘858 patent).
Zhang, USP Indomethacin Suppositories 2019 and the ‘858 patent are listed on the PTO-892 form. English Translation JP 241 is listed on the PTO-892 form.
While claims 8, 11 and 14 are rejected in view of Zhang and USP Indomethacin Suppositories and JP 241, they do not necessarily teach the species of a hard fat such as EUTETOL M®. However, it would be obvious to arrive at the invention of claims 12 and 13 as detailed below.
Regarding claim 12-13 and the limitations where the composition further comprises a hard fat as a base material, the limitation is taught as defined below.
In terms of claim interpretation, an embodiment of the present invention is said to be a suppository indomethacin formulation with EUTECTOL M® hard fat as a base material. See page 1, section FIELD of the Invention.
Further, the specification describes an embodiment of the formulation claimed, indomethacin with hard fat NF at paragraphs Example 1, Table 1 at page 9 of the specification. See also claim Table 2 Example 2 featuring the hard fat EUTECTOL M®.
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In fact, the specification describes EUTECTOL ® hard fat having the limitations of claims 12-13 with regard to the melting point and so forth, along with the claimed CAS Reg. Nos. See page 6, lines 10-15 as detailed below.
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Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the primary reference Zhang 2006 with the claimed indomethacin purity to modify it with the secondary USP Indomethacin Suppositories reference, where the 858 patent discloses use of hard fat (EUTECTOL) as a carrier for anti-arthritis suppositories (for example indomethacin), and JP 241 (also disclosing a hard fat with the claimed hydroxy value) in order to arrive at the claimed invention.
The PHOSITA would have had a reasonable expectation of success because a PHOSITA would have the rationale to combine the known prior art elements of pure indomethacin (a known anti-arthritis drug) and hard-fat with claimed hydroxy value (EUTECTOL) anti-arthritis suppositories so as to predictably arrive at the claimed invention.
Regarding claims 12-13 and the limitation and a suppository of hard fat base material, the 858 patent teaches EUTECTOL® AM as a suppository base. See Column 6, lines 10-30, Example 4, Table 5 below.
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As the specification defines EUTECTOL M® has a hard fat as per claim 6 and the limitations of claims 12-13 are noted to be associated with EUTECTOL®, the teaching of a form of the hard fat EUTECTOL, as by the 858 patent above, used in suppositories will render claims 6 and 12-13 obvious. The rationale to arrive at a finding of obviousness is the combination of known prior art elements according to known methods to predictably arrive at the claimed invention. Here the prior art teaches the combination known elements (use of indomethacin in suppositories as per Zhang and USP Indomethacin suppositories) combined with known methods (per the ‘858 patent use of a form of EUTECTOL in suppositories, where claims 6 and 12-13 are directed to EUTECTOL M® as a hard fat suppository) to predictably arrive at the claimed invention.
Claims 8, 10-11 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. “Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana,” Acta Pharmacologica Sinica 2006 Aug; 27 (8): 1097–1102) in view of USP Indomethacin Suppositories 2019 and Google English Translation JP2005314241 A (JP 241), published Nov 10 2005, accessed April 17 2026, in further view of U.S. Patent 4,681,858 (‘858 patent) and U.S. 3,644,630 A (‘630 patent).
Zhang, USP Indomethacin 2019, 858 patent and 630 patent are listed on the PTO-892 form. English Translation JP 241 is listed on the PTO-892 form.
As noted above, the teachings of Zhang 2006 and USP Indomethacin suppositories and JP 241 render claims 8, 11 and 14 obvious but are silent with regard to the species of claim 10. As detailed above, the 858 patent teaches use of hard fat (EUTECTOL) to be used in hard fat anti-arthritis drug suppositories, where indomethacin is a known anti-arthritic drug. Claim 10 is obvious in further view of US 3644630 A as detailed below.
The ‘630 patent discloses various indomethacin suppositories, where 6.8% to 7.0 % indomethacin is found in a suppository, see Table of column 2.
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With regard to claim 10 and the limitations of indomethacin from about 50 mg to about 100 mg of compound (I) and about 1600 mg of excipient/carrier (Hard Fat NF), it is noted that claim 10 is directed to pharmaceutical compositions where they contain about 3.125% indomethacin (about 50 mg/about 1600 mg) in the suppository to about 6.25% indomethacin (about 100 mg/about 1600 mg) in the suppository.
As per the Table of column 2 above, noting indomethacin concentrations in values of 6.8 to 7.0 %, it would be routine for one of ordinary skill in the art adjust amounts of indomethacin in suppositories to approximate about 100 mg/ about 1600 mg (about 6.25%) as per claim 10. Per MPEP 2144.05 II, the routine optimization of ranges through routine experimentation supports a prima face case of obviousness, citing to In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.")
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the primary reference Zhang 2006 with the claimed indomethacin purity to modify it with the secondary USP Indomethacin Suppositories reference and JP 241, where the 858 patent teaches hard fat are known to formulate anti-arthritis drug suppositories (indomethacin is a known anti-arthritis drug) and 630 patent discloses amounts and concentrations of indomethacin in order to arrive at the claimed invention.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response states the obviousness rejection cannot be maintained because (1) Zhang teaches away from the claimed composition (2) USP 2019 indicate a long felt need in the art, and (3) the combination of the prior art had no reasonable expectation of success.
With regard to points (1) and (2) and the Attorney comments regarding Zhang 2006 and USP 2019 individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
First, the Attorney response states Zhang teaches away from the claimed composition (divergent technology, fungal biotransformation for organic synthesis purposes, not pharmaceutical formulation (formulation design, excipients, storage and pharm. Stability); indomethacin as a metabolic substrate for fungi rather than as a therapeutic agent, etc.).
The Attorney response states Zhang teaches away from the invention, 87.4% of indomethacin is metabolized within 120 hours (Table 2), indicative of chemical instability rather than claimed 99.5% stability after three months of storage of the claimed indomethacin suppository.
In response to applicant's argument that Zhang 2006 is nonanalogous art (divergent fungal biotransformation art), it has been held that a prior art reference must either be in the field of applicant’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the applicant was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, it would have been prima facie obvious to a PHOSITA following the teachings of the primary reference Zhang 2006 with the claimed indomethacin purity to modify it with the secondary USP Indomethacin Suppositories reference in order to arrive at the claimed indomethacin suppository. This is because Zhang is relied upon to arrive at the claimed indomethacin and claimed purity, where USP 2019 and JP 914 are relied upon for their teachings regarding suppositories.
As detailed above, prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the primary reference Zhang 2006 with the claimed indomethacin purity to modify it with the secondary USP Indomethacin Suppositories reference in order to arrive at the claimed indomethacin suppository.
Second the Attorney response argues, USP 2019 in of itself, confirms a long left need in the art which supports a finding of nonobviousness. Specifically, the Response states an Organic Impurities test was deleted from USP 2019. The Attorney argues this establishes that as of December 2019, the pharmaceutical industry lacked a suitable method to control impurities in indomethacin suppositories despite significant commercial and regulatory motivation to solve this problem. Specifically, the Attorney response states the inventive contribution is the identification of specific critical impurities at RRT 0.71 and 1.04 (indomethacin-alpha-monoglycerides) using a novel analytical method using a Gemini C6-phenyl column to resolve these impurities.
MPEP 716.04, which requires use of Declaration to provide evidence of nonobviousness, states the standard for Long-Felt Need and Failure of Others is established when the “I. The Claimed Invention Must Satisfy a Long-Felt Need which was Recognized, Persistent, and Not Solved by Others; II. Long-Felt Need Is Measured from the Date a Problem is Identified and Efforts are Made to Solve it; III. Other Factors.”
While Applicant’s argument states that the deletion of an Organic Impurities test serves as dispositive proof of the long-felt need solved by Applicant, it is noted that this long felt need argued by Applicant is not provided by Declaration evidence per MPEP 716.04.
Declaration evidence which identified the long-felt specific need argued by Applicant, recognized/persistent and not solved by others, where efforts were made to solve it, rather than the Attorney argument conclusion (see MPEP 2145 I.)2 that the deletion of the Organic Impurities test is evidentiary of a secondary consideration long-felt need sufficient to overcome the prima face case of obviousness.
Third, with regard to the invention, the Attorney response argues the claimed combination lacks a teaching, suggestion or motivation and a reasonable expectation of success. Specifically, the Attorney argues the art does not teach the stable suppository and/or purity profile, the specific RRT impurity limitations, or provide guidance of stability under the claimed storage conditions.
As detailed above, prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the primary reference Zhang 2006 with the claimed indomethacin purity to modify it with the secondary USP Indomethacin Suppositories reference in order to arrive at the claimed indomethacin suppository. See also the teachings of English Translation of JP 241 teaching the hard fat and claimed hydroxy value required by claim 8.
The PHOSITA would have had a reasonable expectation of success because a PHOSITA would have the rationale to combine the known prior art elements of pure indomethacin and indomethacin suppositories so as to predictably arrive at the claimed invention.
In response to the Attorney arguments regarding the limitation of “wherein the composition retains at least 99.5% of the compound (I)(% purity) after storage for 3 months at 30±2°C temperature and 65% relative humidity (% RH),” it is pointed out that limitation is directed to a functionally descriptive “storage” property of the pharmaceutical composition defined by the preamble physical description of a storage stable pharm. composition for administration to a body orifice comprising indomethacin with the claimed purity of 99.5% and less than about 0.3% of each individual impurity identified by the claimed RRT measurements by HPLC. Because the physically described limitations of the composition of claim 8 (a storage stable pharm. composition comprising indomethacin with the claimed purity and impurity limitations), the functionally descriptive property of the composition’s purity under the claimed storage conditions would necessarily be present in the prior art teaching claimed composition.
With regard to the Attorney response stating if stability were inherent in combining known elements, commercial products would have met USP standards and the test would not have been deleted, in response, Declarative evidence supporting a long-felt need (secondary consideration to rebut the prima face case of obviousness) would possibly be dispositive in this matter.
Conclusion and Correspondence
In summary no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 “A suppository containing a drug, a hard fat having a hydroxyl value of 10 or less, and glycerin monofatty acid ester or polyglycerin fatty acid ester, the generation of cracks and cracks being suppressed.” See bullet point (1) on page 2.
2 See MPEP 2145. I.ARGUMENT DOES NOT REPLACE EVIDENCE WHERE EVIDENCE IS NECESSARY
Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”). See MPEP § 716.01(c) for examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
Prosecution Insights