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 .
Applicant’s election with traverse of Group I, claims 1-19, and the species of viral infection, in the reply filed on 31 July 2025 is acknowledged.
Claims 1-3 and 15-19 are readable thereon
Applicants’ traversal is based on the assertion that the claims share the special technical feature of treating with Antrodia cinnamomea and the association with ACE-2 enzyme.
However, this is unpersuasive since the technical feature is disclosed in the prior art cited previously within the restriction requirement. Thus the restriction requirement is deemed proper and final.
Note: With respect to claims 20 and 21.
The claims provide for the use of, but, since the claims do not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Furthermore, claims 20 and 21 would be rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
Status of the Claims
Claims 4-14, 20 and 21 are withdrawn.
Claims 1-3 and 15-19 are presented for examination on the merits.
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 1-3 and 15-19 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 inhibition of ACE2 and thus presumably treatment of disorders caused by ACE2 by application of an effective amount of a specific extract of Antrodia Cinnamomum (i.e., AE-F03), does not reasonably provide enablement for any and all treatments and/or prevention of any disease/disorder associated with ACE2 by administering any AC extracts
Please note that the term "prevent" is an absolute definition which means to stop from occurring and, thus, requires a higher standard for enablement than does "treat", especially since it is notoriously well accepted in the medical art that the vast majority of afflictions/disorders suffered by mankind cannot be totally prevented with current therapies - including preventing such disorders as ACE2-associated states such as viral infections (which clearly is not recognized in the medical art as being a totally preventable condition).
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).
Applicant’s claims are drawn broadly to any method of treatment/prevention/reducing the risk of/or alleviating any ACE-2 associated state (e.g, any viral infection) by administering any AC extract. However, the specification provides only one working example, that of an extract of AC with 95%% ethanol as extraction solvent (see paragraph [0060] – [0067]). Regarding the extraction solvent used to obtain the extract product with anti-ACE2 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.
The specification does not provide any specific guidance to show that any and all extracts of AC have the claimed anti-ACE2 functionality. An artisan would have to test every potential extraction technique with the virtually limitless number of solvents. This degree of experimentation clearly places an undue burden on the artisan of ordinary skill. The specification only provides testing data that the extract produced by the extraction procedures and variables disclosed in paragraph [0060] – [0067]. Given the wide range of possible resulting extracts that could potentially result from various extraction methods, the presence of a single example of an extract that possesses anti-anaphylactic properties in a rat intestine in vitro model provides insufficient guidance to the person to practice the invention.
Consequently, given the unpredictability of the art, the lack of guidance from the specification and the quantity of experimentation needed to practice the claimed invention, the claims are not considered to be enabled for every extract of wax bloom (or bloom derived from beeswax) that may have the ability inhibit inflammation.
Claims 1-3 and 15-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the invention had possession, as of the filing date of the application, of the specific subject matter later claimed by him or her. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that the inventor invented the claimed invention.’ Lockwood v. American Airlines, Inc., 107 F. 3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F. 2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, no that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F. 3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient” MPEP § 2163.
Level of Skill and Knowledge in the Art:
The MPEP indicates:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
What constitutes a “representative number” is an inverse function of the skill and knowledge in the art. Satisfactory disclosure of a “representative number” depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly.
However, the specification provides only one working example, that of an extract of AC with 95%% ethanol as extraction solvent (see paragraph [0060] – [0067]). This product with the specific composition was produced by a specific method of extraction from a specific source of AC which could vary considerably. This disclosure is actually a very few number in comparison to the vast number of extracts which could be obtained from beeswax bloom. The reason for this large amount of permutations is because extraction techniques are often coupled in order to obtain a product; for example
1) a water extraction followed by an alcoholic extraction: the product obtained is an extract.
2) a supercritical extraction (CO2 ) followed by an alcoholic and then a non-polar solvent extraction (e.g., chloroform): the product is an extract.
3) a benzene extraction followed by a water extraction and chromatographic separation: the product is an extract.
4) a water/chloroform extraction (e.g., in a seperatory funnel), followed by collection of the water layer, chromatographic separation and crystallization of an isolate: the product is an extract.
5) squeezing the plant to obtain a juice: the product is an extract.
6) dipping the plant in an organic solvent to remove the waxy layer: the product is an 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.
Similarly, as stated previously, the composition of the beeswax from which the bloom is derived and extract obtained will vary greatly depending on the particular source of the beeswax. Since the composition of the beeswax is unpredictable and will defer depending upon the location from which it was obtained (i.e., different pollination sources) as well as the type of bee used to make it, the composition of the bloom will also be unpredictable. Thus the level of skill and knowledge in the art is such that a single example of a particular extract from a particular source of beeswax bloom would not provide sufficient evidence that Applicant is in possession of the claimed invention.
Functional Characteristics Alone or Structure/Function Correlation:
Again, Applicants have not elucidated any phytochemicals in their extracts. Therefore, Applicants have not demonstrated any correlation between the structure of any component which resides in the extract(s) to any particular function. The only composition verified as having the effect as claimed is the extract disclosed by Applicants in their Specification prepared by the specific process of 95% ethanolic extraction of beeswax bloom discussed in paragraph [0060].
Method of Making the Claimed Invention:
Applicants have disclosed only one extraction technique as disclosed in paragraph [0060] of the specification which provide for an extract which has the function of inhibiting ACE2.
Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116).
There is no known means for predicting the capability of other extracts, besides the extract(s) specifically described in the Instant disclosure, with regard to [e.g., anti-ACE2 effect]. The skilled artisan could not even relatively predict what other extracts would perform this function. Absent any discussion regarding correlation between structure and function, even the most skilled of artisans would need to guess what other extracts could potentially have the effect(s) listed in the claim(s).
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 1-3 and 15-19 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 1 is rendered vague and indefinite by the phrase “angiotensin converting enzyme 2 (ACE-2) associated state”. It is unclear how this is meant to define the “state”. That is – how closely “associated” need ACE2 be to the state? Causation? Mechanism of action? It could be interpreted as referring to high or low ACE2 or to diseases occurring concomitantly to the identification of ACE2, etc. The term “associated” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The claim lacks clarity as this functional definition, without giving further instructions in the form of experimental test of testable criteria, does not enable the skilled person to recognize which diseases fall under the claim.
Claim 1 is rendered vague and indefinite by the phrase “Antrodia cinnanmomea extract (Ant-Ex) or fraction 3 thereof (AE-F03)”. It is unclear whether the term Ant-Ex is any Antrodia cinnanmomea extract or is meant to be defined by the specification in paragraphs [0060] and [0064]. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999).
All other claims depend directly or indirectly from rejected claims and are, therefore, also rejected under U.S.C. 112, second paragraph, for the reasons set forth above.
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.
Claim(s) 1-3, and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by any of the following:
Geethangili Madamanchi et al. (2011) discloses Antrodia camphorate (i.e., Antrodia cinnamomea) AC methanolic extract exhibited ACE inhibitory activity. AC significantly reduced oxidative DNA damage, ROS induced by hydrogen peroxide, inhibited antiogenesis, and prevented apoptosis in neuronal-like PC-12 cells. The effects include anti-inflammatory, anti-HBV, abdominal pain, hypertension, viral infection, nephritis, proteinuria, liver cirrhosis, influenza, hepatoma, itchy skin. Ethanol extracts are disclosed.
Liu et al. (US2011/060058) discussed the effects of compounds extracted from A. cinnamomea, including: anti-rheumatism, pain relief, anti-tumor, immune-modulation, anti-allergy, anti-hypertension. Compounds included: sesquiterpene lactone, phenyl and biphenyl compounds from AC; four ergostane-type triterpenoids (anticins E and F and methyl anticinates G and H); two ergostane related steroids, zhankuic acids D and E; three lanosta related triterpenes, 15 alpha-acetyl-dehydrosulphurenic acids, dihydroeburicoic acid and dehydrosulphurenic acid.
CN107648282A [cited by Applicant in IDS filed 10/25/22] discloses 95% ethanol extract of Antrodia cinnamomea’s fruiting body is prepared as product for preventing and/or treating myocardial hypertrophy and/or myocardial fibrosis. Myocardial fibrosis can develop into ischemic heart disease (IHD),and myocardial hypertrophy can develop into chronic heart failure gradually. Myocardial fibrosis is characterized by excessive proliferation of myocardial interstitial fibroblasts (refer to description, paragraphs 0002-0008. 0038-0040).
Note: AC extracts are well known to be possess beneficial effects. Indeed the instant specification point out:
[0003] Previous scientific reports indicated that the Antrodia cinnamomea extracts and purified compounds have numerous biological activities including anti-cancer, anti-inflammatory, hepato- protective, anti-oxidant, neuroprotective and immune-modulatory, and so on. The extracts of Antrodia cinnamomea contains various metabolites including terpenoids, benzenoids, lignans, succinic and maleic acid derivatives, and polysaccharides. Among these, triterpenoids are major components in fruiting bodies, and have received more attention due to their potent anticancer, anti-inflammatory, immunemodulatory, and anti-diabetic properties.
A composition of matter that is old in the art cannot be patented by one who discovers a previously unknown property of that composition. Titanium Metals Corp. of Am. v. Banner, 778 F.2d 775, 227 U.S.P.Q. (BNA) 773 (Fed. Cir. 1985),
For the assessment of novelty it should be taken into account that the mechanism to achieve a therapeutic effect does not render a therapeutic use novel, unless it results is a different treatment, i.e. the treatment of a different patient group.
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) 1-3 and 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over CN107648282A [cited by Applicant in IDS filed 10/25/22]
CN107648282A iscloses 95% ethanol extract of Antrodia cinnamomea’s fruiting body is prepared as product for preventing and/or treating myocardial hypertrophy and/or myocardial fibrosis. Myocardial fibrosis can develop into ischemic heart disease (IHD),and myocardial hypertrophy can develop into chronic heart failure gradually. Myocardial fibrosis is characterized by excessive proliferation of myocardial interstitial fibroblasts (refer to description, paragraphs 0002-0008. 0038-0040).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing dated of the claimed invention to administer Antrodia cinnamomea extracts to treat myriad diseases including those ACE-associated diseases as taught by the cited reference.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
Accordingly, the instant claims, where no unexpected results are observed, would have been obvious to one of ordinary skill having the above cited references before him/her.
Conclusion
No claims are allowed.
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/RUSSELL G FIEBIG/Examiner, Art Unit 1655