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 .
Status of the Claims
Claims 32-50 are pending and under current examination. Claims 1-31 are cancelled.
Information Disclosure Statement
The information disclosure statement filed 9/15/2022 was filed with a size fee assertion and has been considered. An updated, annotated copy has been placed in the application file.
Withdrawn Claim Objections and Rejections
All rejections pertaining to claims 1-31 are moot because the claims are cancelled in the amendments to the claims filed 3/9/2026.
All objections pertaining to claim 32 are withdrawn because claim 1 is cancelled in the amendments to the claims filed 3/9/2026.
All rejections not reiterated have been withdrawn.
Claim Objections
In the claim set filed 3/9/2026, two separate claims were labelled as claim 41 in the list of claims in the Application and this error has been propagated in all subsequent amendments to the claims. Applicant is required to correct the claim number in the next submission. Claims 41 (second incidence)-50 should correspond to claims 42-51 in the correctly numbered claim set. Please be advised that this may affect the claim dependency in some cases as well. The second incidence of claim 41 through claim 50 have been renumbered as 42 and so on.
Claim Rejections - 35 USC § 112
Applicant’s amendments to the claims filed 3/9/2026 have necessitated the new grounds of rejection.
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 37-39 and 48 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.
Claims 37, 38, and 39 recite the limitation “a molar ratio of up to 25:1”, “a molar ratio of up to 3:1”, and “a molar ratio of up to 2:1”, respectively. This renders the claims indefinite because it is not clear what the lower limit of the molar ratio may be.
Claim 48 recites the limitation “a pharmaceutically acceptable salt, ester, derivative, analog, prodrug, hydrate, or solvate thereof”. This renders the claim indefinite because the term “analog” can refer to any compound that can produce the same effect and therefore does not describe structural features of the compound.
Claim Rejections - 35 USC § 103
Applicant’s amendments to the claims filed 3/9/2026 have necessitated the new grounds of rejection.
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 32-40, 42, and 45-51 are rejected under 35 U.S.C. 103 as being unpatentable over Brough (U.S. Patent Application No. 2014/0039031, publication date: 2/6/2014, of record).
Applicant’s Invention
Applicant’s claim 32 is drawn to a method of making a pharmaceutical formulation, the method comprising: processing by thermokinetic compounding (i) an active pharmaceutical ingredient API or a pharmaceutically acceptable salt, ester, derivative, prodrug, hydrate, or solvate thereof, or any combination thereof and (ii) a cyclic oligomer for less than 300 seconds to form an inclusion complex of the API or a pharmaceutically acceptable salt, ester, derivative, prodrug, hydrate, or solvate thereof, or any combination thereof and the cyclic oligomer.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 32, Brough teaches pharmaceutical compositions comprising an API of AKBA, DIM, curcumin, or derivatives thereof [0012]. Cyclodextrins may be present as an excipient to enhance the efficacy and efficiency of the API [0066]. The method of making the pharmaceutical composition is done by thermokinetically processing the API with the one or more pharmaceutically acceptable excipients, adjuvants, or any combination thereof, into a composite [0017]. The API and excipient may be processed by thermokinetic compounding for less than 300 seconds [0020]. With regards to the “inclusion complex” limitation of the instant claim 1, the prior art teaches an identical process for thermokinetic compounding the API and excipient to form a composite and therefore, the inclusion complex is necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “Where the claimed and prior art products are identical or substantially identical in structure or. composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established.”
Regarding claims 33 and 34, Brough teaches that the thermokinetic processing is performed at an average temperature at or below the thermal sensitivity threshold, melting point, glass transition temperature, or the molten transition point of the API, excipients, or adjuvants [0018] and that the pre-defined final temperature, pressure, time of processing and other environmental conditions are selected to substantially eliminate API, excipient, adjuvant, and/or processing agent degradation [0051].
Regarding claim 35, Brough teaches that the thermokinetic compounding process can be performed with or without a processing agent such as an organic solvent [0019].
Regarding claims 36 and 39-40, Brough teaches that the API and one or more pharmaceutically acceptable excipients may be present in a ratio of about 1:2 or 1:3 [0017].
Regarding claim 37, Brough teaches that the API and one or more pharmaceutically acceptable excipients may be present in a ratio of about 1:2 to 1:10 [0017]. The release rate profile of the API is determined by the one or more excipients of the composition [0019].
Regarding claim 42, Brough teaches pharmaceutical compositions comprising an API of AKBA, DIM, curcumin, or derivatives thereof [0012]. Cyclodextrins may be present as an excipient to enhance the efficacy and efficiency of the API [0066].
Regarding claim 45, Brough does not disclose the percentage of API present in the inclusion complex as recited in claim 45. However, the method as claimed is not structurally distinguishable from the disclosure of Brough and therefore, the Examiner has a reasonable basis to believe that the properties claimed in the present invention are inherent in the composition taught by the prior art. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed composition with that of the prior art, the burden of proof is shifted to the Applicants to show an unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art; i.e., to prove that the properties are not inherent. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, USPQ 2d 1922 (PTO Bd. Pat. App. & Int.). As recited in MPEP §2112.01 (II): “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.
Regarding claim 46, Brough teaches that the thermokinetic compounding process can be used for rendering an API amorphous while dispersing in a polymeric, non-polymeric, or combination excipient carrier system and adjuvants [0103]. The compositions may be characterized by XRD measurements [0128]. The Examiner considers the term “amorphous” to read on the “less than 10%...crystalline API” limitation of the instant claim.
Regarding claim 47, Brough teaches that the formulations may contain 25% AKBA, the API, by total weight [0151].
Regarding claim 49, Brough teaches that the thermokinetic compounding process may increase the bioavailability of the pharmaceutical formulations containing AKBA, DIM, curcumin or derivatives or analogs thereof by about 1.5 to about 10 time or more over currently available formulations [0016]. Figures 6 and 6A demonstrate that the API AKBA processed by thermokinetic compounding has an increased AUDC when compared to a commercially available AKBA. The dissolution tests are performed with a dissolution apparatus according to a published USP method [0127].
Regarding claim 50, Brough teaches that the dissolution tests were performed with a VK 7000 Dissolution Tester with a VK 8000 Autosampler. The samples were removed and analyzed for soluble AKBA [0127]. AKBA content may be analyzed by UV-Visible spectroscopy [0018, 0120, and 0122].
Regarding claim 51, Brough teaches that the thermokinetic compounding is performed at a set temperature of 132o or 138oC and an ejection temperature between 151-166oC (Table 3).
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claim 32, Brough does not teach a single embodiment or example meeting all limitation of the invention of claim 32.
Regarding claim 37, Brough does not teach a molar ratio of cyclic oligomer and API within the range of the instant claim.
Finding of a Prima Facia Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claim 32, within the broader scope of Brough all of the limitations of the invention of claim 32 are met. It would have been prima facie obvious for one having ordinary skill in the art to choose the limitations in the instant claims from those disclosed by Brough and arrive at this conclusion because such was contemplated by Brough.
Regarding the molar ratio of cyclic oligomer to the API as specified in claim 37, MPEP 2144.05 states:
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. “[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).
Furthermore, Brough teaches that the release rate profile of the API is determined by the one or more excipients of the composition [0019]. The Applicants' specification provides no evidence that the selected molar ratio in claim 37 was not due to routine optimization and/or that the results should be considered unexpected compared to the prior art. Due to the effect of the excipient on the release rate profile of the API, it would have been prima facie obvious to a person of ordinary skill in the art at the time of the invention to combine these teachings and alter the ratio. One of ordinary skill in the art would have been motivated to change the ratio of excipient and API as this could be expected to be advantageous for optimizing the release rate profile of the API.
Claims 41, 43, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Brough (U.S. Patent Application No. 2014/0039031, publication date: 2/6/2014, of record), as applied to claims 32-40, 42, and 45-51 above, and further in view of Amruta et. al. (Journal of Molecular Structure, pg. 504-510, publication year: 2018), as evidenced by PubChem (2-Hydroxypropyl-Beta-Cyclodextrin, available 2/9/2007).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 41, 43, and 44, Brough teaches pharmaceutical compositions comprising an API of AKBA, DIM, curcumin, or derivatives thereof [0012]. Cyclodextrins may be present as an excipient to enhance the efficacy and efficiency of the API [0066].
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 41, 43, and 44, Brough does not teach a species of cyclodextrin suitable for inclusion in the pharmaceutical composition. However, this deficiency is cured Amruta.
Amruta teaches that inclusion complexes of AKBA and hydroxypropyl-beta cyclodextrin may be made by kneading, co-precipitation, solvent evaporation, and physical mixture (pg. 506, 2.4.1-2.4.4 and Figure 3) and that the inclusion complexation of AKBA with hydroxypropyl-beta cyclodextrin can be used as a simple and useful approach to improve solubility and dissolution performance for enhanced oral bioavailability (pg. 509, Conclusion). PubChem teaches that hydroxypropyl-beta cyclodextrin contains a methyl group (pg. 2, Structure).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art of filing that hydroxypropyl-beta cyclodextrin may be utilized as the cyclodextrin excipient in the composition taught by Brough. One would have understood in view of Amruta that hydroxypropyl-beta cyclodextrin complexed with AKBA improves the solubility, dissolution and oral bioavailability of the drug. It would have been obvious the include the same species of cyclodextrin in the composition taught by Brough. One of ordinary skill in the art of filing would have been motivated to include hydroxypropyl-beta cyclodextrin as the species of cyclodextrin in order to improve the solubility and oral bioavailability of AKBA. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because Amruta teaches that hydroxypropyl-beta cyclodextrin may be complexed with AKBA.
Claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over Brough (U.S. Patent Application No. 2014/0039031, publication date: 2/6/2014, of record), as applied to claims 32-40, 42, and 45-51 above, and further in view of Yocum et. al. (Archives of Internal Medicine, pg. 2947-2954, publication year: 2000).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Brough renders obvious the relevant limitations of claim 32 above. Brough also teaches that the API may include acetyl-11-keto-β-boswellic acid (AKBA), that has been used to treat a number of inflammatory diseases, including osteoarthritis [0008].
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Brough does not teach the inclusion of any API embraced by the instant claim 47. However, this deficiency is cured by Johns Hopkins Arthritis Center.
Yocum teaches that Meloxicam is a safe and effective medication for symptomatic treatment of osteoarthritis (pg. 2947, Abstract)
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (AKBA and meloxicam for the purpose of treating osteoarthritis). See MPEP 2144.06 (II).
Response to Arguments
Applicant's arguments filed 3/9/2026 have been fully considered but they are not persuasive.
On page 10, Applicant argues that there is no motivation in the disclosure of Brough for skilled persons to select a cyclic oligomer from the long list of possible excipients. This is not found persuasive. In response, simply because the prior art “discloses a multitude of effective combinations does not render any particular formulation less obvious." Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). "[P]icking and choosing may be entirely proper in the making of a 103, obviousness rejection." In re Arkley, 455 F.2d 586, 587 (CCPA 1972). Furthermore, it is noted that Applicants do not identify secondary consideration demonstrating criticality or anything unexpected about the inclusion of cyclodextrins in the pharmaceutical formulation.
On pages 10-11, Applicant argues that there is no motivation in the disclosure of Brough for skilled persons to process the cyclodextrin and API by thermokinetic compounding with the expectation of successfully forming an inclusion complex of the API and the cyclic oligomer. This is not found persuasive. In response, the Examiner respectfully refers to MPEP 2112.01 (II) which states: “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established.” The method of producing the pharmaceutical formulation embraced by the instant claims is patentably indistinguishable from the teachings of Brough, therefore the formation of the inclusion complex is inherent in the method of making embraced by Brough. Therefore, the argument is not persuasive and the rejection is maintained.
On page 12, Applicant argues that the statement that “such was contemplated by Brough” in the non-final office action dated 11/2/2025 is unsupported as Brough contemplates neither inclusion complexes nor the specific use of cyclic oligomers to achieve that result. This is not found persuasive. In response, simply because the prior art “discloses a multitude of effective combinations does not render any particular formulation less obvious." Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). "[P]icking and choosing may be entirely proper in the making of a 103, obviousness rejection." In re Arkley, 455 F.2d 586, 587 (CCPA 1972). Furthermore, the Examiner respectfully refers to MPEP 2112.01 (II) which states: “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established.” The teachings of Brough include a method of thermokinetically compounding an API with an excipient, which may be a cyclodextrin. The method of thermokinetically compounding taught by Brough is indistinguishable from the method embraced by the claims, therefore the formation of the inclusion complex is inherent in the teachings of Brough. Therefore, the argument is not persuasive and the rejection is maintained.
Conclusion
No claims are allowed.
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 ELIZABETH ANNE MEYERS whose telephone number is (571)272-2271. The examiner can normally be reached Monday-Friday 8am-5pm ET.
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ELIZABETH ANNE MEYERSExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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