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 .
Claim of Foreign Priority
No claim to foreign priority has been received.
Election/Restrictions
Applicant’s election without traverse of Group III, corresponding to claims 12-22, in the reply filed on June 23, 2026, is acknowledged.
Status of the Claims
Claims 1-22 are pending. Claims 1-11 are withdrawn. Claims 12-22 are examined.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 112
Claims 12-22 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.
Regarding claim 12 and the claims that depend therefrom, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Applicant uses “e.g.” in parenthesis to refer to a second compound. Clarification is requested. It is not clear what compound is being claimed as claim 1 and 12, appear to include a specific compound and a second compound is listed as an example of the first compound. Further, the compound is referred to as a composition.
Clarification is requested.
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 12-22 are rejected under 35 U.S.C. 103 as being unpatentable over Martini et al., “Artemisia annua and Artemisia afra extracts exhibit strong bactericidal activity against Mycobacterium tuberculosis,” Ethnopharmacol. 2020 Nov 15:262 (cited in IDS), in view of Nkunya et al., “Constituents of Artemisia afra,” Fitoterapia (1992), 63(3), 279-80 (Abstract), in view of Watson et al., (WO 03/074146), in view of Sasidharan et al., “EXTRACTION, ISOLATION AND CHARACTERIZATION OF BIOACTIVE COMPOUNDS FROM PLANTS’ EXTRACTS,” Afr J Tradit Complement Altern Med. (2011) 8(1):1-10, and in view of Abubakar et al., “Preparation of Medicinal Plants: Basic Extraction and Fractionation Procedures for Experimental Purposes,” Journal of Pharmacy and Bioallied Sciences Volume 12, Issue 1 January-March 2020.
Martini teaches: “The minimum inhibitory concentrations (MICs) of A. annua and A. afra dichloromethane extracts were determined, and concentrations above the MICs were used to evaluate their ability to kill Mtb and Mycobacterium abscessus in vitro.” Dried leaves of A. annua and A. Afra were resuspended in DCM and extracted for 30 minutes in a sonicating water bath at room temperature. Martini explains the extracts were stronger than artemisinin (AN) alone indicating that other agents are useful for treatment. The plants contain bactericidal compounds in addition to AN. See Abstract. A POSA would undertake steps in view of Martini to isolate and understand which component of A. afra or A. annua is responsible for bactericidal activity other than AN. Processes to do this are standard in the art and they include the claimed steps as set forth below.
Nkunya teaches: “6-Triacontanone, taurin, 5-hydroxy-7,4'-dimethoxyflavone, and 4-methylbenzoic acid were isolated from A. afra.” As evidenced by CAS RN: 5128-44-9/RN (entered 1984) (shown below), the claimed compound has been known since 1984 and is also named 5-Hydroxy-7,4'-dimethoxyflavone.
PNG
media_image1.png
695
772
media_image1.png
Greyscale
Watson teaches a process for preparing extracts of plants. The process comprising providing a natural plant material, extracting with a solvent, subject it to a chromatographic fractionation, and subjecting the process to reversed-phase chromatography, among other steps. See p5, lines 1-15. An extract can isolated and purified through such process to yield a purity of 90 to 99% or higher. See p7, lines 30-31. A plant material can be dried as a starting material. A source of plants can include sources such as Artemisia annua, among others. See p10, line 18. A suitable non-polar solvent that can be used is dichloromethane (DCM), which is particularly preferred. See p11, lines 12-14. Chromatographic fractionation can be used on a comparative scale preferable comprises flash fractionation, such as normal phrase flash fractionation) in conjunction with (i.e., followed by) high performance liquid chromatography (HPLC) such as reverse phase HPLC. See p13, lines 31-33.
Watson also explains that it is routine in the art to readily determine the appropriate column characteristics for chromatographic separation. See p12, lines 4-10. The solvent or mixture used can be determined by routine trial and error using “common, general knowledge” depending on the plant material studied. See p13, lines 25-29.
Watson provides examples in which a dried plant extract is sonicated with DCM. Then, the extract is analyzed using HPLC. Prior art claim 17 includes steps for chromatographic flash fractionation followed by reverse phase HPLC. In one example different elution solvents and/or combinations were used. Methanol was used with increasing amounts of acetone. This was determined to be sufficient to wash off all compounds of interest. See p22, lines 9-12. In another example methanol was used first and then acetone in methanol as an elution gradient. See p22, lines 17-20.
Similarly, Sasidharan teaches extraction, isolation, and characterization of active ingredients in botanicals. The analysis of bioactives involves screening, chromatography, including HPLC, TLC, and others. See Abstract. A general approach includes purification through column chromatography and HPLC to yield a pure compound, followed by structure elucidation procedures, biochemical characterization and then toxicity and in vivo evaluation. See Figure 1. The use of DCM can extract more lipophilic compounds or a mixture of DCM and methanol, and hydrophilic compounds can be extracted with methanol, ethanol, or ethyl-acetate. Hexane can be used to removed chlorophyl. See p2. A number of separation techniques should be used including column chromatography, flash chromatography, Sephadex chromatography, and HPLC, e.g. In the case of dried plant material, an organic solvent such as methanol and chloroform may be used as the initial extract. See p4.
Abubakar teaches preparing medicinal plant extracts typically involve the use of extraction solvents such as: acetone, DCM (intermediate polar) and hexane and chloroform (nonpolar). Solvents are selected in an order of increasing polarity starting from n-hexane to water with the highest polarity. A usually practice is to use a solvent gradient, which include, e.g., using n-hexane and chloroform, then DCM and butanol, and then water, e.g. Large numbers of plants have been extracted, fractionated, and compounds isolated successfully. See p9, final par.
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); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and 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). As such, a POSA would be able to optimize conditions necessary to evaluate the isolates of A. afra including those isolates that are already known.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods in view of Martini, Nkunya, Watson, Sasidharan, and Abubakar. One would be motivated to do so because Martini recognized a component that is bioactive in Artemisia Afra and Artemisia Annua. Nkunya had isolated the claimed compound and identified it as an isolate of Artemisia afra. Further Watson and Sasidharan, as well as Abubakar teach the known methods for isolating, purifying, characterizing, testing for toxicity and in vivo evaluation of active ingredients in botanicals. This includes the use of elution gradients selected based on their polarities. The use of sonication in DCM as an initial step is recognized and preferred and the use of solvents, including hexane to remove chlorophyl as well as methanol, chloroform, and acetone can assist in chromatographic separation of components. Further, the use of chromatographic flash fractionation followed by reverse phase HPLC is taught by Watson and the solvent or mixture used can be determined by routine trial and error using “common, general knowledge” depending on the plant material studied. Moreover, a number of separation techniques are also taught for use by Sasidharan. Thus, the dried plant for analysis was established by Martini and the techniques known for the isolation, purification, and identification of such components are well-known. The ratios of solvents will be optimizable based on the desired to alter the polarity ratio of the solvent combination, e.g. The product isolated will have properties of the isolated product. The sample size does not appear to provide a patentably distinguishing feature. The larger the amount isolated, the larger the sample size. The methods of purification and isolation would appear to yield a product that has a claimed purity. There is a reasonable and predictable expectation of success in isolating and purifying Artemisia annua and Artemisia afra extracts through known methods and techniques and the motivation to do so is the explicit recognition of an active agent other than Artemisinin.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JARED BARSKY/Primary Examiner, Art Unit 1628
Prosecution Insights