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 .
Claims 1-9 are presented for examination on the merits.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
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 1-9 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 administering Bletilla formosana extracts from the solvents and processes and plant parts disclosed and exemplified (i.e., Bletilla formosana (Hayata) Schltr. extract of the present invention named “-W+EA”). and for the in vitro and (intraperitoneally- and intravenously-administered) murine examples, and for the respective exemplified mitigated effects thereof, does not reasonably provide enablement for the treating of the genus of humans or all mammals, for all extracts of B. formosana (and having the recited component compounds), as instantly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Undue experimentation would be required to practice the invention as claimed due to the quantity of experimentation necessary; limited amount of guidance and limited number of working examples provided in the specification; nature of the invention; state of the prior art; relative skill level of those in the art; predictability or unpredictability in the art; and breadth of the claims. In re Wands, 8USPQ2d 1400, 1404 (Fed. Cir. 1988).
The claims are drawn to a method of promoting chronic wound healing by administering to a subject an effective amount of an extract of Bletilla formosana, which, taken together with the specification, imply a breadth greater than supported by the disclosure.
Since the B. formosana extracts (including the solvents and plant part(s) suitable for treating the chronic wounds such as Diabetic foot ulcers remained largely unsolved, means for providing treating of the disease by the administration thereof is highly unpredictable.
Regarding the extraction solvent used to obtain the claims product with anti-inflammatory properties, it is well known in the art that polarity of solvents plays a key role in determining the final product obtained by an extraction. However, because many phytochemicals remain undiscovered, the skilled artisan has to make his/her best educated guess as to what types of phytochemicals will be successfully extracted with a solvent of a particular polarity. Oftentimes, unless the constituents in a particular natural product extract have been well evaluated and documented in the literature, the skilled artisan must adhere to trial and error protocols in order to quantitatively determine phytochemical constituents present in samples obtained from respective extraction procedures. These procedures are common when, for example, a natural product or part thereof has been documented in the literature as possessing some medicinal quality. The skilled artisan will attempt numerous extraction protocols in an attempt to isolate particular ingredient(s) that have medicinal efficacy. Typically, beginning with the first crude extraction, it is a guess as to whether or not the extract will possess certain phytochemical constituents. For example, unpredictability with regard to natural extracts due to their highly complex nature has been well documented. Revilla et al. (J. Agric. Food Chem. (1998), vol. 46, pp. 4592-4597) showed that the slightest variations in polarity of solvent and reaction time upon grape extraction provided respective products with unique characteristic properties (See tables 1, 2, 4, 5, 6 and 7 in Revilla). In turn, each product would possess varying pharmacological properties based upon their respective methods of extraction. Thus, the functional property of an extract of beeswax bloom as an anti-inflammatory is not considered to be predictable because the type of extraction used to produce the extract would have a significant impact on the chemical characteristics of the extract.
There is well-known unpredictability regarding natural product extracts and their e.g., pharmaceutical capabilities. The resulting compositions and thus functional properties of an extraction process are highly dependent on the particular steps of the extraction and the extraction solvent employed
Raskin et al. clearly establish the grave unpredictability of elucidating active ingredients from natural sources:
Multi-component botanical therapeutics also present unique challenges in identifying their active ingredients and in validating their clinical effects. Activity-guided fractionation and reconstitution experiments currently used to characterize compound interferences within a mixture are cumbersome and time consuming…..While chromatographic analysis is often employed to produce biochemical fingerprints used for product comparison…..in the absence of information about the identity of active ingredients, such analysis is hardly reliable, since chromatography provides an incomplete picture of the qualitative and quantitative comparison of a complex extract (p. 3426, col. 2 – p. 3427, col. 1) emphasis added.
The relative skill of those in the art is high. However the treating of the chronic wounds by administering of B. formosana remained beyond the purview of the skilled artisan. Accordingly, one would have turned to the instant disclosure for additional direction and guidance. The amount of direction or guidance presented and the presence or absence of working examples provides limited guidance (see esp. at Examples, tables, and figures, including the solvents and plant parts of B. formosana extracted thereby, the target cell/tissue/organism, and the effects measured resultant of the administering). However, the specification does not provide additional direction and guidance commensurate in scope with the claims.
Thus, considering the state of the art and the high unpredictability and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention for the scope claimed.
It is the Examiner's position that one skilled in the art could not practice the invention commensurate in the scope of the claims without undue experimentation.
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.
Claim(s) 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (2010) in view of Deng et al. (2021).
Wu et al. beneficially teach that Bai ji (Rhizoma Bletillae) is a well known traditional Chinese medicine, and Taiwan bai ji (Bletilla formosana (Hayaata) Schltr.) is commonly available in Taiwan. B. formosana (Hayata) Schltr. was collected from various regions and extracts were prepared. The Folin-Ciocalteu method was used to measure the total phenolic content in extracts. DPPH radical-scavenging assay was employed to measure antioxidant activity. Results showed that the contents of cinnamic acid and militarine in the tubers from Yilan were higher than those in other regions. Moreover, the contents of BHMD and DHMD in the tuber of the plants from Orchid Island were higher than those in other regions. In addition, the content of the components in the seedlings grown by tissue culture were lower.
Therefore the reference teaches that B. formosana extract possess antioxidant activity, but the reference does not explicitly teach treatment of wounds such as diabetic foot ulcers.
Deng et al. beneficially teach that foot ulcers are one of the most common and severe complication of diabetes mellitus with significant resultant morbidity and mortality. Multiple factors impair wound healing include skin injury, diabetic neuropathy, ischemia, infection, inadequate glycemic control, poor nutritional status, and severe morbidity. It is currently believed that oxidative stress plays a vital role in diabetic wound healing. An imbalance of free radicals and antioxidants in the body results in overproduction of reactive oxygen species which lead to cell, tissue damage, and delayed wound healing. Therefore, decreasing ROS levels through antioxidative systems may reduce oxidative stress-induced damage to improve healing. In this context, we provide an update on the role of oxidative stress and antioxidants in diabetic wound healing through following four perspectives. We then discuss several therapeutic strategies especially dietary bioactive compounds by targeting oxidative stress to improve wounds healing.
It would have been obvious to a person of ordinary skill in the art of the instant invention effective filing date to have provided a composition as instantly claimed because the cited references teaches the components were known in the art as useful in a medicinal composition, and administering effective amount of the composition of Bletilla formosana to treat oxidative stress, which is known to play a part in diabetic foot ulcers. From the teachings of cited reference, it is apparent that one of ordinary skilled in the art would have had a reasonable expectation of success in producing the claimed invention.
The cited references are relied upon for the reasons discussed above. If not expressly taught thereby, based upon the overall beneficial teaching provided by this reference with respect to providing therapeutic amounts of the composition in the manner disclosed therein, the adjustments of particular conventional working conditions (e.g., determining one or more suitable dosing and regimens (including amounts/proportions thereof including the amounts as within instant claims 5-7 and ranges in which to perform such a treating therewith and employing common means of administration), is deemed merely a matter of judicious selection and routine optimization which is well within the purview
of the skilled artisan.
From the teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filled. As evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUSSELL G FIEBIG whose telephone number is (571)270-5366. The examiner can normally be reached M-F 8-4.
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/RUSSELL G FIEBIG/Examiner, Art Unit 1655