DETAILED ACTION
Election Acknowledged
Applicant's election with traverse of the invention of Group I encompassing claims 1-25 in the reply filed on 9/5/2025 is acknowledged. The traversal is on the ground(s) that Groups I and II do not pose a serious burden on the examiner as both Groups are interlinked as the method claims are used to make mitragynine free base to which the composition claim is solely directed. This is not found persuasive because as indicated in the restriction mailed 7/15/2025, the Groups may be differently classified in addition to being made in a materially distinct manner such as via supercritical extraction rather than acid-base.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-26 are pending, claim 26 is withdrawn as being directed to nonelected subject matter and claims 1-25 are presented for examination on the merits.
The following rejections are made.
Allowable Subject Matter
Claim 18 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Objections
Claims are objected to because of the following informalities:
Mitragynine is capitalized throughout the claims; see claims 1, 13 and 19-25. Because mitragynine is not a proper noun, it should not be capitalized;
Methylamine, trimethylamine and aniline are currently capitalized in claim 10. These words are not proper nouns and should not be capitalized;
“Vacuum Tray Dryer” is improperly capitalized in claim 18; and
Claim 1(j) and claim 22(j) are missing a “the” between the words “purifying” and “washed”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 14, 17, 20 and 24 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 14 recites, “…wherein in step (j) alcohol is the dilute alcohol.” However, claim 14 and the claims it depends from do not recite “dilute alcohol” and so reference to “the dilute alcohol” is improper. This limitation lacks antecedent basis.
Claim 17 recites, “… the alcohol is 10% methanol”. This is unclear because how can an alcohol be 10% methanol? The alcohol is either methanol or it is not methanol. In the case that the claim is intended to refer to an aqueous 10% methanol solution, then the claim should accurately reflect this. It is also noted that the % does not possess a unit so it is unclear what the % is limiting, e.g. wt., mol, etc. Claim 22(j) is rejected for the same reason.
Claim 20 recites, “…wherein the purity of obtained Mitragynine free base is 47-53% by HPLC.” This limitation “47-53% by HPLC” is unclear. Is this intended to mean that the purity is determined by HPLC? If so, then the claim should be amended to more accurately reflect that. Regardless, the claim is unclear and clarification is requested. Claim 24 is rejected for the same reason.
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 1-8, 10-12, 14-17, 20-22, 24 and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable Xiao et al. (CN 101108872; translation provided) in view of Parthasarathy et al. (Forensic Science International, 2013, 183-187) and Schafer et al. (US 2017/0348222).
Xiao is directed to methods of extracting plant alkaloids.
Xiao’s method comprises combining the plant material (e.g. Solanum nigrum) and with ethanol and an acid (e.g. acetic acid; see instant claims 2 and 3) while stirring (see instant claims 1(a) and (b) and 22(a) and (b)), then filtering and recovering the filtrate (see instant claims 1(d) and 22(d)) (see instant claim 5), purifying the filtrate via resin absorption and then collecting the eluent comprising the plant alkaloid (see instant claims 1(f) and 22(f); note that the receptacle receiving the eluent is being considered ‘the reactor’), precipitating the alkaloid by adding a base (e.g. ammonia; see instant claims 10, 11 and 22) to the eluent such that the added base provides a solution pH of between 8-10 (see instant claims 1(g) and 22(g)), the precipitate containing solution is then stirred (for 20 minutes) and subsequently filtered (see instant claims 1(h) and (i) and 22(h) and (i)) and treated with a diluted organic solution (e.g. 40-80% methanol, 40-70% ethanol; see page 3) (see instant claims 14-16 and 22(j)) for crystallizing/recrystallizing the precipitated product (crystallization/recrystallization is a common technique used for purifying chemical substances) and then collecting the crystalline product (see instant claims 1(j) and 22(j)) (removing the crystal from solution would implicitly result in its drying) (see page 2 and claims 1 and 2). Because the process steps largely overlap with that claimed, the outcome would be expected to yield a free base of the target alkaloid. The purified alkaloid can then be processed into a final dosage form, e.g. grinding, tabletting, etc.
Regarding the alcohol of step (b) of claims 1 and 22, Xiao teaches that the organic solvent used in the extraction step includes various alcohols such as methanol and ethanol (see page 3). It would have been obvious to select methanol for this extraction step with a reasonable expectation for success as methanol is taught to be a suitable alternative of ethanol. See MPEP 2143(I)(E) which states that it is obvious to choose from a finite number of predictable solutions having a reasonable expectation for success. See also MPEP 2144.06(II).
Xiao fails to teach using their extraction method for the purification of mitragynine. Xiao also fails to teach filtering the precipitated alkaloid as obtained from step (h) followed by washing with water.
Parthasarathy is directed to the extraction and quantification of mitragynine, a bioactive alkaloid, from Mitragyna speciosa. The extraction requires the steps of creating a crude mitragynine extract by boiling Mitragyna speciosa (see instant claim 1(a), 22(a) and 25), combining the crude extract with methanol, concentrating the alkaloids from the methanol mixture by evaporating the solvent, adding acetic acid to the methanol extract, separating the alkaloid containing layer from the mixture and adding base so as to increase the pH to 9 at which point the alkaloids were extracted by chloroform. The alkaloid extract was washed with water to remove impurities and then dried (see page 185). As there is substantial overlap in the techniques of Xiao and Parthasarathy, one of ordinary skill in the art would reasonably expect that the use of Xiao’s method on Mitragyna speciosa would be capable of isolating the alkaloid mitragynine from the plant material. See MPEP 2143(I)(A) which states that combining prior art elements according to known method to yield predictable is indicative of obviousness.
Shafer is directed to the extraction of saponin/alkaloid compounds from the Solanum genus of plants such as solanidine and solanine (see [0005, 0038]). Example 1 describes a method wherein the plant is mixed with an ethanol solution (see instant claim 5) and then filtered to remove plant matter and collect the supernatant. The removed plant matter is then combined a citric acid solution (see instant claims 2 and 3) and then filtered to remove plant matter and collect supernatant. The ethanol and acid supernatants are then combined and stirred (see [0066]) (see instant claims 1(a), (b) and (d) and 22(a), (b) and (d)). The mixture is then filtered and the supernatant collected and centrifuged to remove unwanted contaminating material. The collected solution is then made alkaline by addition of sodium hydroxide sufficient to achieve a pH of 10 (see [0067]) so as to form a precipitate of the alkaloid compounds (see instant claims 1(f), (g) and (h) and 22(f), (g) and (h)). The precipitate is then isolated by filtration (see [0068]) and washed with water (see [0041, 0069]) (see instant claims 1(i) and 22(i)). The washed precipitate is then combined with an alcohol, concentrated by evaporation and dried (see [0069, 0070]) (see instant claims 1(j) and 22(j)). Regarding the obviousness of the washing step, MPEP 2143(I)(C) which states that the use of a known technique (washing an alkaloid precipitate with water to remove impurities) to improve similar methods (extraction of alkaloids) in the same way is supportive of obviousness.
Regarding step (c) of claims 1 and 22, the step of “adding water to the mixture of (b) while continuously stirring” is considered obvious as the medium of “the mixture” is water. Xiao’s mixture (b) is an acidified aqueous solution of the alcohol alkaloid extract. Adding additional water to an already aqueous mixture undergoing stirring is not considered inventive as the result would simply be the dilution of the mixture without changing the relative amounts of the reagents. That is the components of the mixture would still be present in the same relative quantities and capable of performing the same chemistry in solution. Moreover, step 1(c) is silent regarding the amount of water added relative to the mixture being stirred. Absent some showing otherwise, the addition of water during the stirring process step is not seen as materially impacting the extraction process.
Regarding the time frame and speed of stirring as recited by instant claims 4, 7, 8, 12 and 22, these are considered obvious as the references generally describes stirring the mixtures throughout the extraction process. Although Xiao teaches that stirring may be performed for between 10 to 30 minutes, the reference is silent to the speed of stirring and time period of stirring together. However, such parameters would have been obvious to optimize given the general principle of stirring being taught by Xiao. Identifying speed of stirring and a suitable time frame for the stirring would have been an obvious next step. If it were found that 15-30 minutes of 30-50 rpm yielded a suitable process for purifying the target substance, then such would have been the product of ordinary skill and common sense. See MPEP 2144.05(II)(A) which states that where the general conditions of a claim are described in the prior art, it is not inventive to discover optimum ranges by routine experimentation.
Regarding instant claims 17 and 22(j), Xiao teaches using 40-70% methanol in their ‘purification’ process. Although the reference does not teach a 10% methanol solution, such would have been obvious as it is sufficiently close to expect similar results. See MPEP 2144.05(I) regarding the obviousness of approaching and similar amounts/proportions. See also MPEP 2144.05(II)(A) regarding optimization where general conditions are known.
Regarding instant claims 20 and 24, assuming that the purity is determined by HPLC (see 112(b) above), Xiao teaches that their extraction process is capable of recovering alkaloid with an extraction purity of 90% (see abstract), Parthasarathy teaches that their mitragynine extraction process yields mitragynine with a purity of about 96% as measured by HPLC (see page 186) and Shafer similar. A purity of between 47-53%, although less than that achieved by the prior art, would have certainly been within the scope of the prior arts capabilities if so desired. The purity of a substance is not determinative of patentability. See MPEP 2144.04(VII).
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Claims 19 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Xiao et al. (CN 101108872; translation provided) in view of Parthasarathy et al. (Forensic Science International, 2013, 183-187) and Schafer et al. (US 2017/0348222) as applied to claims 1-8, 10-12, 14-17, 20-22, 24 and 25 above, and further in view of Sanchez-Soto et al. (J Am Ceram Soc, 83, 7, 1649-1657).
As previously noted, Xiao teaches that the purified alkaloid crystal is to be ground into a powder.
Xiao, Parthasarathy and Tewari fail to teach the purified mitragynine material as being amorphous.
Sanchez-soto teaches that crystalline materials that undergo grinding become a powder that is disordered and amorphous. Thus, grinding a crystalline material destroys the crystalline structure and results in an amorphous material (see abstract and page 1655). The powderized material of Xiao would therefore become an amorphous and in the case of mitragynine, the grinding of the purified crystallized mitragynine would result in an amorphous mitragynine.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Claims 9 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Xiao et al. (CN 101108872; translation provided) in view of Parthasarathy et al. (Forensic Science International, 2013, 183-187) and Schafer et al. (US 2017/0348222) as applied to claims 1-8, 10-12, 14-17, 20-22, 24 and 25 above, and further in view of Bernabe et al. (US 2009/0247727).
Xiao and Schafer describe filtering, in general, the extract mixtures at points (d) and (i) of claims 1 and 22.
However, the references fail to teach the specific filter steps of (d) filtering through a nutsche filter of 5 microns and (i) filtering via centrifuge with 200-250 RPM using 5 micron filter cloth.
Bernabe is directed to the purification of dianhydrides which uses various filtration techniques such as centrifugal filtration, filter press, nutsche filtration, rotary drum filter and/or belt filter wherein the filtration technique uses a filter have a pore size of between 5-10 micrometers (see [0059]). The filter medium may be cloth (see [0059]). Given that the prior art describes filtering the extraction solutions at the same points as that claimed, one of ordinary skill would be capable of identifying known methods of filtration and using them at points (d) and (i) with a reasonable expectation for success. Thus, the selection of a nutsche filter and a centrifuge filter using a pore size of 5 microns would have been an obvious parameter to optimize given that the pore size determines how filtered the end product is to be. Moreover, the speed of the centrifuge during the filtration step would be a parameter that one of ordinary skill in the art would endeavor to optimize so as to find the best speed for achieving a filtered end product. If such an undertaking of optimization identified a speed of between 200-250 RPM, then that finding would have been a product of ordinary skill and common sense rather than one of innovation.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Potentially Relevant Prior Art
Goh et al (Molecules, 26, 2021, 1-16)
Tewari et al. (US2019/0330203)
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE A PURDY whose telephone number is (571)270-3504. The examiner can normally be reached from 9AM to 5PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Bethany Barham, can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE A PURDY/Primary Examiner, Art Unit 1611