DETAILED ACTION
This office action is in response to applicant’s filing dated October 14, 2025.
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 Claims
Claims 1-11 are pending in the instant application. Acknowledgement is made of Applicant's remarks filed October 14, 2025.
Election/Restrictions
Applicant’s election without traverse of a formulation species comprising Brevilin A and a lipophilic solubilizer, Labrafac CC and the inflammatory disease species, hair loss, in the reply filed on October 14, 2025 is acknowledged.
Claims 3 and 8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 14, 2025.
Claims 1, 2, 4-7, and 9-11 are presently under examination as they relate to the elected: Brevilin A, Labrafac CC, and hair loss
Priority
The present application is a 371 of PCT/KR2021/011534 filed on August 27, 2021, which claims benefit of foreign priority to Republic of Korea 10-2020-0142792 filed on October 30, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 28, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, except where marked with a strikethrough.
Drawings
Acknowledgement is made of the drawings received on April 28, 2023. These drawings are accepted.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Claim Rejections - 35 USC § 112(b)
Indefinite
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 7 and 8 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.
Claim 7 contains the trademark/trade names BRIJ 010-SS-(RB), Capryol 90, Capryol PGMC, Gantrez ES-435, Gantrez S-97 BF, Gelucire 43/01, Gelucire 44/14, Gelucire 50/13, Gelucire 48/16, Labrafac CC, Labrafac Lipophile WL1349, Labrafac PG, Labrafil M 1944 CS, Labrafil M 2125 CS, Labrafil M 2130 CS, Lauroglycol 90, Lauroglycol FCC, Monosteol, Peceol, Pharmasolve, Plurol Oleique CC497, Span 20-LQ-(SG), Span 60-PA-(SG), upper Refined Oleic Acid-LQ-(JP), Super Refined Tween 80A-LQ-(MH), Surfadone LP-300, Transcutol HP, Transcutol P, TWEEN 60-SS-(SG), TWEEN 80 HP-LQ-(MH), TWEEN 80-LQ-(SG), Vitamin E TPGS, Miglyol 812, and captax 355.
Claim 7 contains the trademark/trade names Labrasol, Crodex A-PA-(RB), Geleol, Gelot 64, Suppocire AS2X, Suppocire BML, Synperonic PE/F 127,Synperonic PE/L 44, and Tefose 63.
Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademarks/trade names is used to identify/describe various lip and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 112(a)
Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 4-7, and 9-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating hair loss comprising administering a composition comprising a Centipeda minima extract comprising Brevilin A, does not reasonably provide enablement for a method of preventing and treating any inflammatory disease and autoimmune disease and non-alcoholic fatty liver disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention relates to a method of preventing and treating any inflammatory disease and autoimmune disease and non-alcoholic fatty liver disease comprising administering to the subject a composition comprising a Centipeda minima extract comprising Brevilin A.
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain). As illustrative of the state of the art, the examiner cites Freire et al (Periodontol 2000, 2013; 63(1):149-164), Tabas et al (Science, 2013; 339(6116):166-172), Hu et al (Curr Top Med Chem, 2019; 19:1-13), and Iliev et al (J Med Chem, 2025; 68:9501-9524).
Freire, cited for evidentiary purposes, teaches inflammation is an essential mechanism in human health and disease (page 149, 1st paragraph); inflammation is initiation as a protective response to challenges or foreign bodies, or injury, experienced by host tissues. Thus, by broadest reasonable interpretation any injury or disease is an inflammatory disease.
Tabas, cited for evidentiary purposes, teaches a number of widespread and devastating chronic diseases, including atherosclerosis, type 2 diabetes, and Alzheimer’s disease, have a pathophysiologically important inflammatory component; in these diseases, the precise identity of the inflammatory stimulus is often unknown and, if known, is difficult to remove; although there has been success with anti-inflammatory therapy in chronic diseases triggered by primary inflammation dysregulation or autoimmunity, there are considerable limitations; in particular, the inflammatory response is critical for survival; as a result, redundancy, compensatory pathways, and necessity narrow the risk:benefit ratio of anti-inflammatory drugs (Abstract).
Moreover, with regard to inhibiting or suppressing JAK-STAT signaling, Hu, cited for evidentiary purposes, teaches after more than two decades of development, STAT3 has developed into a potential therapeutic target for cancer therapy, although many small molecule inhibitors have been developed targeting STAT3 and achieved good results at both cellular and animal models; however, FDA has not approved the drugs for the target STAT3, so the development of small molecule inhibitors still faces great challenges (page 7, left, last paragraph). Hu teaches it is interesting to note that STAT3 is involved in both tumor and inflammation, and STAT3 regulates a variety of target genes; the activation of STAT3 is also regulated by many factors; because STAT3 is involved in a number of regulatory factors, inhibition of STAT3 can also lead to a number of side effects, which makes the development of STAT3 inhibitors into clinical drugs has encountered difficulties (page 7, right).
Moreover, Iliev teaches (STAT3) is a promising yet challenging anticancer drug target due to its complex signaling and limited “druggability” (Abstract); canonically, the STAT3 signaling cascade entails cytokine or growth factor stimulation, which leads to the activation of receptor complexes that recruit and phosphorylate STAT3; phosphorylated STAT3 monomers then form homodimers and translocate to the nucleus where they promote the expression of pro-tumorigenic and antiapoptotic gene signatures; over the past few decades, a much more complex picture of STAT3 signaling has emerged, where different activation patterns, dimerization and oligomerization partners, dimer orientations, activators, coactivators, and deactivators have been identified; accordingly, the STAT3 signaling cascade is found at the center of many cellular processes, with several upstream activators (cytokines and growth factors) and mediators (kinases and phosphatases) as well as a myriad of downstream gene targets; while these findings often highlight the important role of STAT3 in promoting and maintaining cancerous phenotypes, the broad and far-reaching roles of STAT3 in cellular and oncogenic processes makes evaluating the specific actions of potential STAT3 inhibitors immensely challenging (page 9501, left). Moreover, Iliev teaches while many small-molecule STAT3i have been reported in the literature, the lack of clinical progress of such agents as anticancer therapies continues to drive innovation in drug discovery efforts within the STAT3i field (page 9511, right, last paragraph).
These articles plainly demonstrate that the art of developing and testing drugs, particularly for use in humans, is extremely unpredictable, particularly in the case of a single compound or genus of compounds being used to treat any and being used to treat any and all inflammatory disease and autoimmune disease and non-alcoholic fatty liver disease even agents targeting the JAK-STAT pathway.
2. The breadth of the claims
Claims 1, 2, 4-7, and 9-11 are very broad in terms of the type of diseases being treated: all types of inflammatory disease and autoimmune disease and non-alcoholic fatty liver disease are claimed to be treated with a Centipeda minima extract comprising Brevilin A. Moreover, the instant claims do not require the composition to be administered in an effective amount to a subject in need thereof. Without a subject in need thereof, the method encompasses a healthy subject without the disease.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides examples of a Centipeda minima extract comprising Brevilin A in subjects suffering from androgenetic alopecia (Example 1). However, the specification does not provide any data that shows that a Centipeda minima extract comprising Brevilin A is useful for treating and preventing any inflammatory disease and autoimmune disease and non-alcoholic fatty liver disease, other than for treating hair loss.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that a Centipeda minima extract comprising Brevilin A could be predictably used as treatment or preventative for all inflammatory disease and autoimmune disease and non-alcoholic fatty liver disease, other than for treating hair loss. Since there is no precedent in the literature for the treatment of any inflammatory disease and autoimmune disease and non-alcoholic fatty liver disease with a Centipeda minima extract comprising Brevilin A, except for hair loss, how is the skilled physician supposed to know what type of dose regimen of a Centipeda minima extract comprising Brevilin A to use for each of the pathologically different diseases?
Determining if a Centipeda minima extract comprising Brevilin A will treat any particular disease state would require formulation into a dosage form, and subjecting into clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of claims 1, 2, 3-8, 10-17, and 20 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 2 and 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al (Processes 2020, 8: 767 pp 1-14).
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Regarding claims 1, 2, 9, and 10, Kim teaches the study aims to evaluate whether the emulsion extract of brevilin A from Centipeda minima (CMX) stimulates hair regrowth in a clinical trial, as a JAK3 inhibitor, combined with network pharmacology-based analysis; CMX showed potent inhibition of JAK3 in a concentration-dependent manner; significant differences in total hair count, terminal hair count, and anagen hair count from the baseline to 24 weeks were observed between the placebo and CMX subjects; and study suggests that the medicinal herbal extract CMX is useful in the treatment of mild to moderate vertex balding that contribute to the visible improvements in hair growth observed in treated patients (abstract). Kim teaches seventy-two patient with active mild to moderate hair loss in the vertex area enrolled in the study; thirty-two (1 man and 31 women, 88.9%) placebo-treated subjects and thirty-four (1 man and 33 women, 94.4%) CMX-treated group completed the 24-week study; age, total hair count, terminal hair count, and anagen hair count were similar at baseline; significant differences in total hair count, terminal hair count, and anagen hair count from the baseline to 24 weeks were observed between the placebo and CMX subjects (page 8, last paragraph); and the CMX group showed higher total hair count, terminal hair count, and anagen hair count than the placebo group (page 9, 1st paragraph). Thus, Kim teaches a method of treating hair loss in a subject comprising administering a Centipeda minima extract comprising brevilin A, wherein the Brevilin A inhibits JAK-STAT signaling process.
Regarding claim 11, Kim teaches patients were randomized to receive 0.5 mL of CMX (1% brevilin A microemulsion tonic) (page 4, 5th paragraph).
MPEP 2131.03 states:
"[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (citing In re Petering, 301 F.2d 676, 682, 133 USPQ 275, 280 (CCPA 1962)).
In the instant case, an amount of 1% falls within the instant claimed range of claim 11 and thus anticipates the claimed range of claim 11.
Thus, the teachings of Kim anticipate the method of claims 1, 2, and 9-11.
Claims 1, 2, 9, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang et al (WO 2019/168348 A1).
WO 2019/168348 A1 (Yang) is the PCT counterpart to US 2021/0138011 A1 (Yang). WO 2019/168348 A1 has a 102(a)(1) date as a result of its September 6, 2019 publication date. Because WO 2019/168348 A1 and US 2021/0138011 A1 appear to have identical disclosures, and because the WO document was published in Korean language designating the United States, the US 2021/0138011 A1, which is the National Stage entry of WO 2019/168348 A1, is being used as a translation of WO 2019/168348 A1. As such, any reference hereinafter to column and line numbers will be based upon the US publication, but should be interpreted as referring to the corresponding disclosure of the aforementioned WO counterpart.
Regarding claims 1, 9, and 10, Yang teaches a method of treating hair-loss comprising administering a therapeutically effective amount of a Centipeda minima extract or a fraction thereof to a subject in need thereof (claim 1). A Centipeda minima extract reads on a composition comprising a Centipeda minima extract comprising Brevilin A as evidenced by Chan et al (J Pharm Biomed Anal, 2016; 125:400-407). Chan teaches qualitative and quantitative analysis of chemical constituents of Centipeda minima (Title); and brevilin A is one of 2 compounds found to be the most abundant in the ethanol extract of EBSC (Centipeda minima) (abstract).
Regarding claim 2, Brevilin A inhibits JAK-STAT signaling process as evidenced by Chen et al (PLOS One, 2013; 8(5):e63697 pp 1-11). Chen teaches Brevilin A exhibited both strong STAT3 signal inhibition (Abstract).
Thus, the teachings of Yang anticipate the method of instant claims 1, 2, 9, and 10.
Claims 1, 2, 4-7, and 9-11 are rejected under 35 U.S.C. 102(a)(1) or 102(a)(2) as being anticipated by Pyo et al (WO 2020/141891 A1).
The applied reference has a common Assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
WO 2020/141891 A1 (Pyo) is the PCT counterpart to US 2022/0073484 A1 (Pyo). WO 2020/141891 A1 has a 102(a)(1) date as a result of its July 9, 2020 publication date and 102(a)(2) date as a result of its January 2, 2020 filing date. Because WO 2020/141891 A1 and US 2022/0073484 A1 appear to have identical disclosures, and because the WO document was published in Korean language designating the United States, the US 2022/0073484 A1, which is the National Stage entry of WO 2020/141891 A1, is being used as a translation of WO 2020/141891 A1. As such, any reference hereinafter to column and line numbers will be based upon the US publication, but should be interpreted as referring to the corresponding disclosure of the aforementioned WO counterpart.
Regarding claims 1, 2, 9, and 10, Pyo teaches throughout the literature, it has been reported that brevilin A is a major ingredient of Centipeda minima [0052]; brevilin A may suppress or inhibit JAK-STAT signaling, thereby showing an effect on treatment of autoimmune diseases such as alopecia premature, traction alopecia, alopecia areata, alopecia neurotica, pityroid alopecia, malignant alopecia, female pattern alopecia, male pattern alopecia, androgenic alopecia, telogen alopecia, alopecia totalis, genetic hair loss, alopecia universalis or the like ([0053] and [0081]). The disclosed products may be effective in ameliorating various diseases wo which the effect of brevilin A may be applied including autoimmune diseases such as alopecia premature, traction alopecia, alopecia areata, alopecia neurotica, pityroid alopecia, malignant alopecia, female pattern alopecia, male pattern alopecia, androgenic alopecia, telogen alopecia, alopecia totalis, genetic hair loss, alopecia universalis or the like[0081]. Thus, Pyo teaches a method of treating hair loss comprising administering a Centipeda minima extract comprising brevilin A.
Regarding claims 4 and 11, Pyo teaches examples containing brevilin A in amounts of 33.54% and 80.69%.
Regarding claim 5, Pyo teaches a method for extracting a non-polar natural substance comprising conducting an extraction of a natural raw material to prepare a primary liquid extract; mixing the primary liquid extract with a phase separation composition containing a lipophilic solubilize (claim 1); wherein the non-polar natural substance comprises brevilin A (claim 3) and the natural raw material is Centipeda minima (claim 5).
Regarding claims 6 and 7, Pyo teaches the lipophilic solubilizer includes the elected Labrafac CC [0073].
Thus, the teachings of Yang anticipate the method of instant claims 1, 2, 4-7, and 9-11.
Claim Rejections - 35 USC § 103
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.
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 4-7 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al (WO 2019/168348 A1) in view of Ye et al (KR2014120508A, translation obtained from the Global Dossier); Chen et al (PLOS One, 2013; 8(5):e63697 pp 1-11); and Pyo et al (WO 2020/141891 A1).
Regarding claims 4 and 11, as set forth above, Yang teaches a method of treating hair-loss comprising administering a therapeutically effective amount of a Centipeda minima extract or a fraction thereof to a subject in need thereof (claim 1). Yang does not teach the Centipeda minima extract comprises 30 to 90% by weight of Brevilin A.
However, Ye teaches the disclosed compounds inhibit the activity of signal transducer and activator of transcription 3 (stat3) (claim 6); the composition comprising the compounds are used for treating stat3-related disease is alopecia greata (claim 9). Thus, Ye establishes that it was known in the art that a method of inhibiting stat3 is useful for treating alopecia.
Chen teaches Brevilin A exhibited both strong STAT3 signal inhibition (Abstract).
Pyo teaches throughout the literature, it has been reported that brevilin A is a major ingredient of Centipeda minima [0052]; brevilin A may suppress or inhibit JAK-STAT signaling, thereby showing an effect on treatment of autoimmune diseases such as alopecia premature, traction alopecia, alopecia areata, alopecia neurotica, pityroid alopecia, malignant alopecia, female pattern alopecia, male pattern alopecia, androgenic alopecia, telogen alopecia, alopecia totalis, genetic hair loss, alopecia universalis or the like ([0053] and [0081]); Examples containing brevilin A in amounts of 33.54% and 80.69%.
As such, Yang teaches a method of treating hair-loss comprising administering a therapeutically effective amount of a Centipeda minima extract or a fraction thereof; since Ye teaches a method of inhibiting stat3 is useful for treating alopecia; since Chen teaches that Brevilin A inhibits stat3; since Pyo teaches brevilin A is a major ingredient of Centipeda minima; brevilin A inhibits JAK-STAT signaling and is useful for treating hair loss, and Examples containing brevilin A in amounts of 33.54% and 80.69%, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yang to administer the brevilin compositions taught by Pyo with an expectation of success, since the prior art establishes that Centipeda minima extract and inhibiting stat3 is useful for treating alopecia, brevilin A is major component of Centipeda minima extract, brevilin A inhibits stat3, and extracts comprising brevilin A are useful for inhibiting JAK-STAT signaling and treating hair loss.
Regarding claim 5, Pyo teaches a method for extracting a non-polar natural substance comprising conducting an extraction of a natural raw material to prepare a primary liquid extract; mixing the primary liquid extract with a phase separation composition containing a lipophilic solubilize (claim 1); wherein the non-polar natural substance comprises brevilin A (claim 3) and the natural raw material is Centipeda minima (claim 5).
Regarding claims 6 and 7, Pyo teaches the lipophilic solubilizer includes the elected Labrafac CC [0073].
Taken together, all this would result in the method of claims 4-7 and 11 with a reasonable expectation of success.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al (WO 2019/168348 A1) in view of Ye et al (KR2014120508A, translation obtained from the Global Dossier); Chen et al (PLOS One, 2013; 8(5):e63697 pp 1-11); and D’Amelio et al (US 5,804,206).
Regarding claim 11, as set forth above, Yang teaches a method of treating hair-loss comprising administering a therapeutically effective amount of a Centipeda minima extract or a fraction thereof to a subject in need thereof (claim 1). Yang does not teach the Centipeda minima extract comprises brevilin A in the amounts of instant claim 11.
However, Ye teaches the disclosed compounds inhibit the activity of signal transducer and activator of transcription 3 (stat3) (claim 6); the composition comprising the compounds are used for treating stat3-related disease is alopecia greata (claim 9). Thus, Ye establishes that it was known in the art that a method of inhibiting stat3 is useful for treating alopecia.
Chen teaches Brevilin A exhibited both strong STAT3 signal inhibition (Abstract).
D’Amelio teaches a process for obtaining a plant extract comprising providing a plant material of the Centipeda genus, sequentially macerating and extracting said plant material with a plurality of aqueous-ethanolic solvents (claim 1), wherein the Centipeda plant material is from Centipeda minima (claim 2). D’Amelio further teaches combining extract solutions with an effective amount of glycerol to prevent precipitation of compounds from solution (claim 21). D’Amelio teaches the extract is preferably diluted with 20% ethanol to obtain a final concentration of 0.2% sesquiterpene lactones calculated as Brevilin A; the extract further contains about 3% by volume glycerol (col 6, lines 38-41).
As such, Yang teaches a method of treating hair-loss comprising administering a therapeutically effective amount of a Centipeda minima extract or a fraction thereof; since Ye teaches a method of inhibiting stat3 is useful for treating alopecia; since Chen teaches that Brevilin A inhibits stat3; since D’Amelio teaches extracting brevilin A to produce a therapeutic wherein the Brevilin A, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yang to administer the brevilin compositions taught and obtained by D’Amelio with an expectation of success, since the prior art establishes that Centipeda minima extract and inhibiting stat3 is useful for treating alopecia, brevilin A is major component of Centipeda minima extract, brevilin A inhibits stat3.
Taken together, all this would result in the practice of the method of claim 11 with a reasonable expectation of success.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 4-7, and 9-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-13 of copending Application No. 18/575,351 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims are directed to a method of preventing or treating inflammatory disease and autoimmune diseases and non-alcoholic fatty liver disease in a subject comprising administering a composition comprising a Centipeda minima extract comprising at least one selected from the group consisting of Brevilin A, Arnicolide D, Arnicolide C, and Michrohelenin C as an active ingredient to the subject wherein the disease includes the elected species hair loss.
The copending claims a functional composition for hair loss containing a functional ingredient for hair loss, a diluent, a surfactant, a co-surfactant; a moisturizer; and an emulsifier, wherein the functional ingredient is selected from Brevilin A, Arnicolide D, Arnicolide C, and Michrohelenin C, wherein the amounts of Brevilin A, Arnicolide D, Arnicolide C, and Michrohelenin C overlap the instantly claimed amounts. The diluent and surfactant of the copending claims are the same or very similar to the instantly claimed lipophilic solubilizer and surfactant.
Thus, It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to arrive at the instantly claimed method from the copending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 2, 4-7, and 9-11 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628