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 .
Election/Restrictions
As a clarification, the grouping of claims in the invention groups should delineate Group I to contain claim 9 and Group II to contain claims 1-8 and 10. Applicant’s election without traverse of group II in the reply filed on June 20, 2026 is acknowledged.
The requirement, as clarified, is still deemed proper and is therefore made FINAL.
Claim 9 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Objection
Claim 1 is objected to because of the following informalities: A modification of claim 1 to recite “conducting a reaction within mixed solution A …” or something similar instead of “conducting a reaction…” to clearly require the recited reaction to occur in the mixed solution A.
Appropriate correction is required.
Claims 2, 4, and 6-8 are 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, any intervening claims, and any clarifying modifications.
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.
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.
Claim 10 is 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.
The claim recites in its preamble “a method of manufacturing a medicament”; however, the only active step is “using the vascular embolic agent”. This verbiage equates to a “use claim” which merely recites a use without any active, positive steps delimiting how this use is actually practiced (see MPEP2173.05(q)). This absence of recited steps makes the scope of the claim unclear.
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.
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 1 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (CN 1141772238 – English translation cited for citations) in view of Endo et al. (Macromolecules 2006 39: 4038-4043), Li et al. (Fitoterapia 2020 144(104605):1-7), and Cody et al. (US Patent No. 5,916,590) as evidenced by Wu et al. (Journal of Natural Products 2010 73:1898–1906).
Liu et al. teach the preparation of a pharmaceutical product for treating benign prostatic hyperplasia (see page 1 first paragraph). The process combines lipoic acid (1, 2 dithiolane), resveratrol (polyphenol), pumpkin seed oil (organic solvent), isoflavones (polyphenol), lycopene, as well as traditional Chinese medicine extracts, then mixes the combination with heating and stirring at 70 to 80⁰C to dissolve components into the oil and form a mixture (see page 6 last partial paragraph-page 7 first full paragraph and example 5). They teach the temperature and stirring to be important for reaction in the mixture (see (see page 7 first full paragraph). Liu et al. describe the traditional Chinese medicine extracts as made from raw materials that are a combination that includes Melia toosendan (Chinaberry) fruit due to its analgesic and anti-inflammatory properties. They go on to teach incorporation of the finished mixture into a soft gelatin capsule (see example 5). Additionally, Liu et al. exemplify different proportions of pumpkin seed oil (organic solvent) and lipoic acid in the compositions, where one example has a higher proportion of the pumpkin seed oil and lower concentration of lipoic acid (e.g. dilution) than another (see example 1 vs example 2). The heating duration of the product and a description of the heating and mixing vessel are not detailed.
Endo et al. teach the heat/melt induced reaction of lipoic acid via melting the material at 80⁰C in a sealed vessel and incubating for 6 hours (see abstract and page 4038 second column last full paragraph and table 1).
Li et al. teach that the fruit of Melia toosendan (Chinaberry) is employed for its analgesic properties and includes alkaloid compounds as some of its main bioactive compounds (see page 1 first and Wu et al. page 1098 first column first paragraph).
Cody et al. teach loading a heated pharmaceutical fill material into a soft capsule and cooling the fill material to room temperature (see abstract and column 4 lines 41-57).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a Chinese traditional medicine extract in the lipoic acid containing mixture of Liu et al. that contains the alkaloid compounds of Melia toosendan (Chinaberry) because they are key bioactive compounds of this component, as taught by Li et al. It also would have been obvious to perform the mixing and heating step of Liu et al. in a sealed vessel for 6 hours in light of Endo et al. This modification would have been obvious because this methodology was known for conducting a similar heat/melt based lipoic acid reaction and provides a known vessel for performing a similar heat/melt based reaction. The modification is also obvious as the application of the same technique to a similar product in order to yield the same improvement or the simple substitution of one known element for another in order to yield predictable outcome. Further, Liu et al. contemplate the reacted lipoic acid mixture at “diluted” concentrations in organic solvent. There is no evidence that adding the organic solvent in two portions (e.g., organic solvent A and organic solvent B are the same) before and after reaction yield an unexpected difference as compared to the full amount of solvent being adding in one portion before reaction. This piece-wise addition appears to equate to a different order of adding ingredients, given that the overall amount of organic solvent is the same at the end of the method, regardless of whether it is added as one larger portion or as two smaller portions. MPEP 2144.04IVC highlights In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946), noting that the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Additionally, it would have been obvious to cool the reacted mixture to room temperature during the course of assembly with the soft capsules of Liu et al. in light of Cody et al. who also teach a heated fill material that is loaded into soft gelatin capsule. The modification is obvious as the application of the same technique to a similar product in order to yield the same improvement (e.g. cooled pharmaceutical product ready for administration). Therefore claims 1 and 10 are obvious over Liu et al. in view of Endo et al., Li et al., and Cody et al. as evidenced by Wu et al.
Claims 1, 3, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. in view of Endo et al., Li et al., and Cody et al. as evidenced by Wu et al. as applied to claims 1 and 10 above, and further in view of Wang et al (CN 103768327 – English translation referenced for citations).
Liu et al. in view of Endo et al., Li et al., and Cody et al. as evidenced by Wu et al. render obvious the limitations of instant claims 1 and 10. Liu et al. teach that the mass ratio of lipoid acid (1,2 dithiolane) to resveratrol (polyphenol) + isoflavones(polyphenol) to alkaloid containing traditional Chinese medicine extract is 1 to 0.35 to 0.15 (see example 5; instant claim 3). Further, Liu et al. exemplify the proportion of the pumpkin seed oil (organic solvent) to range from about 30 to 45 wt% of the lipoid acid mixture/product (see example 1-5, as calculated by the examiner). While the ratio of 1, 2-dithiolane to polyphenol meets the instantly claimed limitations, the proportion of alkaloid in the traditional Chinese medicine extract is not detailed.
Wang et al. teach a traditional Chinese medicine extract that contains alkaloids and is produced from a combination of raw materials that includes Melia toosendan fruit (see abstract). Different types of compounds, such as alkaloids, flavones, and saponins, are extracted in different solvents that are recombined into a final extract (see paragraphs 11 and 25-29). The proportion of alkaloid in the extract is taught to vary based upon the ratios of recombined solvent extraction solvents, where their final extract has a range of alkaloid that spans from about 2 to about 60 wt% (see page 2 last paragraph as calculated by the examiner).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the extraction procedure of Wang et al. on the raw traditional Chinese medicine extract components of Liu et al. so as to yield the medicinal mixture. The proportion of alkaloid in the extract would then vary and yield a range that, when applied to the traditional Chinese medicine extract portion of the 1 to 0.35 to 0.15 mass ratio of 1,2-dithiolane to polyphenol to alkaloid containing traditional Chinese medicine extract, would yield alkaloid proportions that overlap or embrace the instantly claimed range (e.g., 2 to 60% of 0.15 = 0.003 to 0.09, as calculated by the examiner). Instant claim 3 recites the mass ratio of organic solvent A to mixed solution as (2-4):10 and the organic solvent B to vascular embolic agent as (1-5):10. When organic solvents A and B are the same, this equates to a final organic solvent proportion that ranges from 25 to 70 wt% (as calculated by the examiner). This range also overlaps with the range of about 30 to 45 wt% organic solvent provided by Liu et al. “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)” (see MPEP 2144.05). The evidence of record does not reflect an unexpectedly superior outcome due to the claimed selection of the component proportions. Therefore claims 1, 3, and 10 are obvious over Liu et al. in view of Endo et al., Li et al., and Cody et al., and Wang et al. as evidenced by Wu et al.
Claims 1, 5, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. in view of Endo et al., Li et al., and Cody et al. as evidenced by Wu et al. as applied to claims 1 and 10 above, and further in view of Miao (CN 101040902– English translation referenced for citations).
Liu et al. in view of Endo et al., Li et al., and Cody et al. as evidenced by Wu et al. render obvious the limitations of instant claims 1 and 10, where a traditional Chinese extract is included amongst the reactants to produce a composition that treats benign prostatic hyperplasia. Lipoic acid, resveratrol, and isoflavone are present. The presence of leonurine is not detailed.
Miao teaches a traditional Chinese extract composed of alkaloids from motherwort, also known as Leonurus japonicus, for treating benign prostatic hyperplasia (see paragraphs 2-4). The alkaloids of interest include leonurine (see paragraph 4; instant claim 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add the traditional Chinese medicine extract of Miao to the reaction mixture of Liu et al. in view of Endo et al., Li et al., and Cody et al. as evidenced by Wu et al. The modification is obvious as the application of the same technique to a similar product in order to yield the same improvement. In addition, the modification also results in two traditional Chinese medicine extracts for benign prostatic hyperplasia being present in combination. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (see MPEP 2144.06). Therefore claims 1, 5, and 10 are obvious over Liu et al. in view of Endo et al., Li et al., and Cody et al., and Miao as evidenced by Wu et al.
Relevant Prior Art
Chen et al. (previously cited) teach the reaction of the claimed combination of lipoic acid (1, 2-dithiolane), tannic acid (polyphenol), and tromethamine (called TRIS base; alkaloid) that are dissolved in a solvent to produce an injectable wound healing adhesive gel (see table 1 and page 1795 second column first full paragraph-page 1796 first partial paragraph). The solution is heated to 70⁰C and incubated at this temperature for 60 seconds, then cooled to and through room temperature (see page 1795 second column first full paragraph-page 1796 first partial paragraph). The reaction time is significantly shorter than that instantly claimed. Several 1,2-dithiolane to polyphenol to alkaloid ratios, such as 1:0.3:0.5, are disclosed and the solvent proportion ranges from 50 to 55 wt% of the compositions and falls within the 25 to 70 wt% provided in the composition made by the instantly claimed method. The solvent of Chen et al. is water, not an organic solvent, and the procedure is touted for its green synthetic characteristics and speed (see page 1795 first partial paragraph).
Solvents other than water are known to be preferred for green chemistry, including ethanol. Dimethyl sulfoxide (DMSO) is known to be useable in green chemistry, but less suited than water or ethanol (see Calvo-Flores et al. Topics in Current Chemistry 2018 376(18):1-40)). Ethanol as a solvent for lipoic acid reactions is known to be purposefully included to run the reaction at a room temperature which is below that instantly claimed (see Wang et al. (Wang B) Advanced. Functional. Materials 2021 31(2101494): 1-11, page 2 first column last partial paragraph). Further, DMSO has been employed for melt induced lipoic acid reactions, as in Chen et al., and melt induced lipoic acid reactions were also known to run in a sealed vessel for 6 hours (see Jiang et al. CN 109897200 - English translation referenced for citations, paragraphs 9 and 64; Endo et al. abstract and page 4038 second column last full paragraph and table 1). However, it is not clear that a significantly longer reaction time and change to DMSO, a less “green” solvent, would not be destructive to the intent of Chen et al. or alter the properties of the final product, due to the longer reaction, such that it no longer functions as they desire. Similarly, a change of solvent to ethanol paired with the required elevated temperature also does not appear to be fully supported.
Other claimed polyphenols such as catechol were known to be reacted with lipoic acid via melt induced reaction, however, solvent-less reactions were employed (see Cai et al. ACS Applied Materials and Interfaces 2021 13:53083−53090).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARALYNNE E HELM whose telephone number is (571)270-3506. The examiner can normally be reached Mon-Fri 9-5.
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/CARALYNNE E HELM/Examiner, Art Unit 1615
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