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 .
Status of Claims
Clams 55 – 74 are pending.
Clams 1 – 54 are cancelled.
Claims 55 – 74 are rejected.
Claim Rejections - 35 USC § 112 (Written Description)
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.
Claims 68 – 74 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 MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. 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, not 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 “ determining whether the application describes an actual reduction to practice of the claimed invention, 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 and 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. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
I. Scope of claims
In the instant case: Claim 68 is broadly drawn to a method of treating or preventing any infection with a microbial agent by administering to a subject a composition defined by claim 64 as zingerone as the microbial agent.
In the instant case: Claim 72 broadly identifies a microbial organism being selected from any bacteria or any fungi.
II. Scope of Disclosure
Reduction to practice:
The only disclosure is for the preparation of zingerone via the processing of ginger root and juice and/or marc obtained from ginger root by treating with and alkaline solution. The obtained zingerone from the process is combined with the antibiotics gentamicin, vancomycin and cefotaxime. Gentamicin is an antibiotic in the class of aminoglycosides and is used to treat severe gram-negative bacterial infections. It is available in a range of dosage forms including injectable solution, as well as intravenous and oral formulations. Vancomycin is an antibiotic in the class of glycopeptides and is the most widely used glycopeptide antibiotic for treating gram-positive infections in adults, children, and neonates. Cefotaxime belongs to the cephalosporin family of antibiotics.
Microbial infections are caused by harmful pathogen. Specifically, bacteria, viruses, fungi, and parasites. Treating microbial infections depends on the specific type of microbe; such as, bacteria, viruses, or fungi.
The types of treatment include antibiotics, antivirals and antifungals. Antibiotics are used for certain bacterial infections like strep throat or urinary tract infections; available as pills, creams, or IV drips. Antivirals and antifungals are specific medications designed to slow or stop viruses or fungi when applicable. Viral infections are treated with vaccines and are distinct from bacterial infections, which require antibiotics.
The disclosure does not show that the Applicant provided screening in vitro and in vivo to determine which combination of antibiotics, antivirals and antifungals with zingerone would exhibit the desired antibiotics, antivirals and antifungals activity. Specifically, zingerone combined with any known antibiotics, antivirals and antifungals, that will be capable of treating or preventing any form of microbial infection caused by any form of bacteria or type of fungi.
According to test discussed in Applicant’s Example 7, it was determined that gentamicin combined zingerone and vancomycin combined with zingerone reduced the MIC for Staphylococcus aureus as compared to gentamicin, vancomycin, and zingerone added individually (see Figures 9A-9B). For the combination of zingerone and gentamicin, this activity was synergistic: FICI = 0.5 = (MICA combi 4 µg/mL /MICA alone 16 µg/mL) + (MICB combi 6.25 mg/g /MICB alone 25 mg/g). For the combination of zingerone and vancomycin, the inhibitory activity was significantly increased, and nearing synergistic activity: FICI = 0.1 = (MICA combi 4 µg/mL /MICA alone 8 µg/mL) + (MICBᶜᵒᵐᵇi 12.5 mg/g /MICB alone 25 mg/g). By comparison, the combination of zingerone and cefotaxime did not produce any notable change in activity when compared to each compound applied individually.
It is generally known in the medical and pharmaceutical industry that treating human microbial infections is becoming less predictable due to antimicrobial resistance (AMR), delayed diagnostics and pathogen persistence. The pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833,166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute.
Level of skill and knowledge in the art:
The relative level of skill possessed by one of ordinary skill in the art of medical research is relatively high, as a majority of lead investigators directing scientific research and development in this particular technological area possess an Ph.D. in a scientific discipline such as organic synthetic chemistry, polymer chemistry, medicinal chemistry, biochemistry, pharmacology, biology, a microbiologist, bacteriologist or virologist or the like
III. Analysis of the Fulfillment of the Written Description Requirement
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that claim(s) 68 is broad and generic, with respect to all possible infections caused by bacteria or fungi, as well as the combination of zingerone with any form of antibiotics, antivirals and antifungals encompassed by the claims. Although the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the composition beyond those compositions specifically disclosed in the examples in the specification. Moreover, the specification lacks sufficient variety of species to reflect this variance in the genus of the compositions and the microbial infections to be treated and/or prevented with the composition as claimed. While having written description of the process for preparing zingerone from the process and combining with the antibiotics gentamicin, vancomycin and cefotaxime, the specification does not provide sufficient descriptive support for the myriad of microbial infections and treatments with antibiotics and antifungals embraced by the claims. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 112 (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.
Claims 68 – 74 are rejected under 35 U.S.C. 112(a), because the specification, while being enabling for treatment of bacterial infections caused by Staphylococcus aureus bacterial, does not reasonably provide enablement for a method of treating or preventing any infection with a microbial agent by administering to a subject a composition of zingerone as the microbial agent, or zingerone in combination with any of antibiotics, antivirals and antifungals. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The test for enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States v. Telectronice, 8, USPQ2D 1217 (Fed. Cir, 1988). Whether undue experimentation is needed is not based upon a single factor but rather in a conclusion reached by weighing many factors. The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention:
In the instant case: Claim 68 is broadly drawn to a method of treating or preventing any infection with a microbial agent by administering to a subject a composition defined by claim 64 as zingerone as the microbial agent.
In the instant case: Claim 72 broadly identifies a microbial organism being selected from any bacteria or any fungi.
(2) the scope of the claims:
a) Scope of the composition: The composition is zingerone.
b) Scope of the infection: any infection that may be caused by any bacteria or any fungi.
Common Bacterial Infections: streptococcal, staphylococcal, tuberculosis, gonorrhea, chlamydia, Lyme disease, salmonella, pneumonia, whopping cough, diphtheria, cellulitis, impetigo, abscesses, campylobacter, cholera, shigellosis, Buruli ulcer, meningitis and listeriosis to name a few.
Types of fungal infections: candidiasis, onychomycosis, ringworm, tinea versicolor, sporotrichosis, chromoblastomycosis, eumycetoma, aspergillosis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis, and pneumocystis pneumonia.
(3) The state of the prior art:
The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific diseases and by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
Kumar et al. discloses the combination of zingerone and ciprofloxacin for the inhibition of biofilm formation and biofilm eradication suggesting potential therapeutic value in treating P. aeruginosa biofilm infections with this combination (Abstract, 4. Discussion, Fig. 4 & 5, & Conclusion). (Fitoterapia, 2013. 90).
Kumar et al. discloses the use of zingerone for potentiating the antimicrobial effect of azithromycin, gentamicin, amikacin, carbenicillin, ceftazidime, ciprofloxacin, and cefotaxime (Abstract, Materials and Methods, & Results). (Life Science, 2014, 117).
Hosseinzadeh et al. discloses the administration of zingerone, administered orally in an amount of 10 mg/kg, to 200 g rats (providing a 2 mg dose) co-administered with gentamicin for the prevention of gentamicin induced nephrotoxicity. (Abstract, Materials and Methods). Gentamicin has both antibacterial and some antifungal activity. (Comparative Clinical Pathology, 2020, 29).
(4) The predictability or unpredictability of the art:
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity, in re Fisher, 166 USPQ 18 indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute.
(5) The relative skill of those in the art:
The relative level of skill possessed by one of ordinary skill in the art of medical research is relatively high, as a majority of lead investigators directing scientific research and development in this particular technological area possess an Ph.D. in a scientific discipline such as organic synthetic chemistry, polymer chemistry, medicinal chemistry, biochemistry, pharmacology, biology, a microbiologist, bacteriologist or virologist or the like
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The specification has provided guidance for combining zingerone with the antibiotics gentamicin, vancomycin and cefotaxime. According to test discussed in Applicant’s Example 7, it was determined that gentamicin combined zingerone and vancomycin combined with zingerone reduced the MIC for Staphylococcus aureus as compared to gentamicin, vancomycin, and zingerone added individually (see Figures 9A-9B). For the combination of zingerone and gentamicin, this activity was synergistic: FICI = 0.5 = (MICA combi 4 µg/mL /MICA alone 16 µg/mL) + (MICB combi 6.25 mg/g /MICB alone 25 mg/g). For the combination of zingerone and vancomycin, the inhibitory activity was significantly increased, and nearing synergistic activity: FICI = 0.1 = (MICA combi 4 µg/mL /MICA alone 8 µg/mL) + (MICBᶜᵒᵐᵇi 12.5 mg/g /MICB alone 25 mg/g). By comparison, the combination of zingerone and cefotaxime did not produce any notable change in activity when compared to each compound applied individually.
Applicant is claiming a method for treating and preventing any infection with a microbial agent. Wherein the microbial agent is a composition of zingerone or a composition of zingerone and any antibiotics, antivirals and antifungals.
However, other than what is provided in Example 7, the specification does not provide data to show that there was any screening of specific bacterial infections, viral infection or fungal infections, in vitro or in vivo, to determine what combination of zingerone with antibiotics, antivirals and antifungals would exhibit the desired activity. The Applicant has failed to describe any in vitro and in vivo screening of any representative number of patients suffering from any type of infection, whether bacterial, viral or fungal .
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to the variety of bacterial and viral infections desired to be treated and prevented with the zingerone composition or zingerone in combination with the hundreds of antibiotics, antivirals and antifungals claimed and the high unpredictability in the art as evidenced therein, 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 commensurate in the scope of the claims.
Genetech Inc. v. Novo Nordisk A/S 42 USPQ2d i001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable".
Therefore, in view of the Wands factors and In re Fisher discussed above, to practice the claimed invention herein, one of skill in the art would have to engage in undue experimentation to test which infections can be treated or prevented by the zingerone composition or zingerone in combination with the hundreds of antibiotics, antivirals and antifungals compound encompassed in the instant claims, with no assurance of success.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 72 and 74 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 72 recites the limitation "the microbial organism" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 74 recites the limitation "the microbial infection" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim.
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) 64 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Connell et al. (Aust. J. Chem., 1979, vol. 22, no. 5).
The rejected claim covers, inter alia, zingerone.
Connell discloses zingerone. (abstract, pp. 1034 compound (I)).
Applicant is reminded that claim 64 is claimed in a Product-by-Process format. MPEP §2113 reads, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.”
It is well settled that the presence of process limitations in product claims, which product does not otherwise patentably distinguish over the prior art, cannot impart patentability to that product. The addition of a method step in a product claim, which product is not otherwise patentably distinguish over the prior art, cannot impart patentability to that old product." SmithKline Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1318 (Fed. Cir. 2006) (quoting In re Stephens, 345 F.2d1020, 1023 (CCPA 1965).
The PTO takes the following position with respect to Product- by-Process claims, As stated in ln re Thorpe, 777 F.2d 695, 697, 698,227 USPQ 964, 966 (Fed. Cir. 1985): Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.
In Examination, “the structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221,223 (CCPA 1979). "The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Additionally, once the Examiner establishes that a product, recited in terms of its process of making, is prima facie unpatentable due to anticipation, Appellants bear the burden of proving "that the prior art products do not necessarily or inherently possess the characteristics of his claimed product." Id. at 698 (quoting In re Fitzgerald, 619 F.2d 67, 70 (CCPA 1980); In re Best, 562 F.2d 1252, 1255 (CCPA 1977)).
Accordingly, applicant's claim is considered a product claim, and the process steps do not have any weight, if the product is known over prior art. In this case the product or composition is known from Connell. Therefore, the claim is anticipated by the prior art.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 55, 56, 59, 60, 63, 64 and 65 are rejected under 35 U.S.C. 103 as being unpatentable over Xiaosheng (CN106673981). (see English translation).
The rejected claims cover, inter alia, a method of producing zingerone, comprising:(i) subjecting ginger root to an alkaline treatment in an alkaline solution; or (ii) subjecting juice and/or marc obtained from ginger root to an alkaline treatment in an alkaline solution; thereby producing zingerone.
Dependent claim 56 further limits the ginger root or juice. Dependent claim 59 further limits the temperature conditions for alkaline treatment. Dependent claim 60 further limit the length of time for the alkaline treatment. Dependent claim 63 further limits the zingerone.
Rejected claim 64 discloses a zingerone composition. Dependent claim 65 further limits the zingerone composition.
However, Xiaosheng discloses a method for extracting effective components of fresh gingers. Xiaosheng discloses processes for the production of zingiberone (i.e. zingerone) comprising cutting the ginger into slices, mixing with ammoniacal liquor (i.e. an alkaline solution), and extracting for 2 hours at 45°C. The resulting material is centrifuged, concentrated by distillation, to afford zingiberone (Example 1). The resulting composition is suitable as a pharmaceutical composition since Xiaosheng explicitly teaches the zingiberone residual ammonia solution is "nontoxic to the human body". (pp. 5). In Example 1: Plant polyphenol extract per 30g of raw material taken from the apple into 100ml 90 ° C deionized water leaching 1h, filtered, the filtrate is the plant polyphenol extract, spare. A method for extracting ginger active ingredients, the steps are as follows: (1) Ginger cut into pieces, crushed into ginger; (2) The ginger obtained in the step (1) is mixed with ammonia water with a mass concentration of 5% of the extractant, then the above-mentioned spare plant polyphenol extract is added, and the extract is ionized and extracted for 2 hours while maintaining the temperature at 45° C; wherein, the ionization is the pass voltage of 0.1 V is extracted by ionization; wherein, ginger and ammonia water, the above spare plant polyphenol extract mass ratio of 1: 1: 0.01, namely ginger: ammonia: the spare plant polyphenol extract = 1: 1: 0.01 mass ratio; and (3) After the step (2) is ionized, the obtained material is centrifuged, the supernatant is taken, the mixture is distilled at 36° C for 1.5 hours, the ammonia solution is recovered and concentrated to a water content of 30% at 30° C to obtain zingerone. 40%. (pp. 1 – 4).
The difference between Xiaosheng and the claimed invention is that it does not teach the invention with particularity so as to amount to anticipation (See M.P.E.P. §2131: "[t]he identical invention must be shown in as complete detail as is contained in the ...claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).).
However, based on the above, Xiaosheng teaches the elements of the claimed invention with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. (see M.P.E.P. § 2143).
Claim Rejections - 35 USC § 103
Claim(s) 55, 56, 60, 61, 64 and 65 are rejected under 35 U.S.C. 103 as being unpatentable over Hongmei et al. (CN 113156019) ( see English translation).
The rejected claims cover, inter alia, a method of producing zingerone, comprising:(i) subjecting ginger root to an alkaline treatment in an alkaline solution; or (ii) subjecting juice and/or marc obtained from ginger root to an alkaline treatment in an alkaline solution; thereby producing zingerone.
Dependent claim 56 further limits the ginger root or juice. Dependent claim 60 further limit the length of time for the alkaline treatment. Dependent claim 61 further limits the method steps.
Rejected claim 64 discloses a zingerone composition. Dependent claim 65 further limits the zingerone composition.
However, Hongmei discloses Hongmei discloses a composition comprising Zingiberis rhizome (i.e. Ginger root) is pulverized (considered to include "chopping" of the root) and treating with water containing 0. 1M NaOH at an extraction temperature of 95°C for a 60 minute interval followed by two 30 minute intervals (Example 1, step 2). This extract is then concentrated in vacuo followed by methanolic extraction to obtain the test solution (Example 1, step 3). Additionally, compositions comprising zingerone solubilized in 50% methanol are disclosed (Example 1, Part 2 "Preparation of reference solution"). The solution extracted following alkaline treatment is considered suitable as a pharmaceutical composition. In the translation gingerone is another name for zingerone. (pp. 5 – 8).
The difference between Hongmei and the claimed invention is that it does not teach the invention with particularity so as to amount to anticipation (See M.P.E.P. §2131: "[t]he identical invention must be shown in as complete detail as is contained in the ...claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).).
However, based on the above, Hongmei teaches the elements of the claimed invention with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. (see M.P.E.P. § 2143).
Claim Rejections - 35 USC § 103
Claim(s) 64, 65, 66, 67, 68, 69, 70, 71 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Hosseinzadeh et al. (Comparative Clinical Pathology, 2020, 29).
The rejected claim 64 covers, inter alia, a composition of zingerone.
Applicant is reminded that claim 64 is claimed in a Product-by-Process format. MPEP §2113 reads, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.”
Dependent claim 65 further limits the composition. Dependent claim 66 limits the dosage of the zingerone in formulation. Dependent claim 67 further limits the administration of the zingerone with an anti-microbial agent.
Claim 68 discloses a method for treating or preventing an infection by administering composition of zingerone. Dependent claim 69 further limits the form of the composition of zingerone being administered. Dependent claim 70 further limits the dosage the composition of zingerone being administered. Dependent claim 71 further limits the administered composition of zingerone to be co-administered with one or more anti-microbial agents. Dependent claim 72 discloses that a microbial organism being treated.
However, Hosseinzadeh discloses the administration of zingerone, administered orally in an amount of 10 mg/kg, to 200 g rats (providing a 2 mg dose) co-administered with gentamicin for the prevention of gentamicin induced nephrotoxicity (Abstract, & pp, 972 Materials and Methods, rt. col. “Study design and groups”). The composition administered was in liquid form. Gentamicin (GEN) is described as an aminoglycoside antibiotic widely used against severe gram-negative infections. (pp. 971, rt. col. ln 9 – 11). Zingerone (ZIN) has several pharmacological effects including antioxidant, anti-inflammatory, and free radical scavenging activity. (abstract). Hosseinzadeh does not explicitly disclose the prevention of bacterial or fungal infection using this combination, the prevention of both microbial infections is considered an inevitable result in the administration of the combination of zingerone and gentamicin (as gentamicin has both antibacterial and some antifungal activity).
The difference between Hosseinzadeh and the claimed invention is that it does not teach the invention with particularity so as to amount to anticipation (See M.P.E.P. §2131: "[t]he identical invention must be shown in as complete detail as is contained in the ...claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).).
However, based on the above, Hosseinzadeh teaches the elements of the claimed invention with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. (see M.P.E.P. § 2143).
Claim Rejections - 35 USC § 103
Claim(s) 64, 65, 67, 68, 69, 71, 72, 73 and 74 are rejected under 35 U.S.C. 103 as being unpatentable over Kumar et al. (Fitoterapia, 2013. 90).
The rejected claim 64 covers, inter alia, a composition of zingerone. Applicant is reminded that claim 64 is claimed in a Product-by-Process format. MPEP §2113 reads, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.”
Dependent claim 65 further limits the composition. Dependent claim 67 further limits the administration of the zingerone with an anti-microbial agent.
Claim 68 discloses a method for treating or preventing an infection by administering composition of zingerone. Dependent claim 69 further limits the form of the composition of zingerone being administered. Dependent claim 71 further limits the administered composition of zingerone to be co-administered with one or more anti-microbial agents. Dependent claim 72 discloses that a microbial organism being treated. Dependent claim 73 further limits the bacteria.
However, Kumar et al. discloses the combination of zingerone and ciprofloxacin for the inhibition of biofilm formation and biofilm eradication suggesting potential therapeutic value in treating Pseudomonas aeruginosa (P. aeruginosa) biofilm infections with this combination (Abstract, 4. Discussion, Fig. 4 & 5, & Conclusion). In Kumar, it is reported that the National Institute of Health (NIH) reported that about 80% of all microbial infections are caused by biofilms. P. aeruginosa causes many types of chronic biofilm-associated infections such as keratitis, burns, wound infections, respiratory and urinary tract infections which are responsible for significant morbidity and mortality. (pp. 73, rt. col. last para. to pp. 74 left col. ln 3). Biofilm formation by P. aeruginosa was significantly reduced in the presence of sub lethal concentration of zingerone. Combined therapy of zingerone with ciprofloxacin showed significantly high biofilm inhibition and biofilm eradication activity. (pp. 78, Conclusion).
The difference between Kumar and the claimed invention is that it does not teach the invention with particularity so as to amount to anticipation (See M.P.E.P. §2131: "[t]he identical invention must be shown in as complete detail as is contained in the ...claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).).
However, based on the above, Kumar teaches the elements of the claimed invention with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. (see M.P.E.P. § 2143).
Claim Rejections - 35 USC § 103
Claim(s) 55 – 63 are rejected under 35 U.S.C. 103 as being unpatentable over Lapworth et al. (Journal of the Chemical Society Transactions, 1917, vol. 111) in view of Connell et al. (Aust. J. Chem., 1979, vol. 22, no. 5) and Nomura (Journal of the Chemical Society, Trans. 1917, vol.111)
The rejected claims cover, inter alia, a method of producing zingerone, comprising:(i) subjecting ginger root to an alkaline treatment in an alkaline solution; or (ii) subjecting juice and/or marc obtained from ginger root to an alkaline treatment in an alkaline solution; thereby producing zingerone.
Dependent claim 56 further limits the ginger root or juice. Dependent claim 57 further limits the alkaline solution to potassium hydroxide (KOH). Dependent claim 58 further limits the alkaline solution to calcium hydroxide (Ca(OH)2). Dependent claim 59 further limits the alkaline treatment temperature. Dependent claim 60 further limit the length of time for the alkaline treatment. Dependent claim 61 further limits the method steps. Dependent claim 62 further limits the extraction steps. Dependent claim 63 further limits the zingerone.
However, Lapworth discloses the isolation of various constituent components of ginger by extracting ginger with aqueous alcohol solutions, treatment with "milk of lime" (i.e. saturated Ca(OH)₂ solution), neutralization, separation of the organic portion from the aqueous layer, followed by drying and concentration under vacuum (pp. 778, "Method Used in Isolating Gingerol"). Lapworth then discloses the isolation and identification of zingerone, produced by steam distillation and further proposes that this ketone may be readily obtained from the extract of ginger by decomposition of gingerol using hot baryta water (i.e. a solution of Ba(OH)₂) followed by treatment with ether (pp. 783 - 784, "Action of Heat and of Hydrolytic Agents on Gingerol. Formation of Aliphatic Aldehydes (mainly n- Heptaldehyde) and a Ketone, "Zingerone."). Lapworth identified the properties of the new ketone, C11H14O3, and noted that it dissolved freely in dilute aqueous sodium or potassium hydroxide, and reprecipitated by carbon dioxide. (pp. 785, para. 3).
The difference between Lapworth and the instantly claimed invention is as follows: obtaining zingerone from ginger root or juice from the ginger; alkaline solution of KOH or Ca(OH)2; alkaline treating temperature; and supercritical fluid extraction.
However, regarding obtaining zingerone from ginger root or juice from the ginger, the Examiner turns to the teaching of Lapworth and Connell. Both Lapworth and Connell do not treat ginger root or juice from the ginger but treat gingerols isolated from ginger. Connell obtained gingerols from sliced dried ginger that was ground and packed in glass columns. Acetone was allowed to percolate overnight to yield the extract. The ground ginger was described as dried marc. The extract was concentrated, diluted with water and the pH was adjusted with sodium carbonate solution. The extract was treated to isolate and subjected to purification to obtain the gingerol. (Connell, pp. 1040 Experimental section, (b), (c) and (d)). Connell is further examination of the process of type discloses in Lapworth. Also, it is noted the in Applicant’s disclosure the juice is describe as containing gingerol (Applicant’s Example 4, [0248]). Further, it well known in the prior art that fresh ginger does not contain zingerone. Connell discloses that is formed by the action of alkalis or heat on gingerol or the oleoresin. (Abstract).
Thus, even though the is no reference to ginger root or juice from the ginger, based on Connell gingerol is obtained from dried ginger root, and it is the alkaline treatment of gingerol that forms zingerone As such, it would have been obvious to one having ordinary skill in the art before the effective date of the instantly claimed invention. to obtain ginger root or juice from the ginger and directly treat those items because the action on the gingerol therein produces the zingerone. Motivation for using the ginger root or juice from the ginger can be found in a desire to enhance commercial opportunities by making the process cheaper and faster.
With regard to alkaline solution of KOH or Ca(OH)2, and alkaline treating temperature; the Examiner turns to the teaching of Lapworth, Connell and Nomura. Lapworth then discloses the isolation and identification of zingerone, produced by steam distillation and further proposes that this ketone may be readily obtained from the extract of ginger by decomposition of gingerol using hot baryta water (i.e. a solution of Ba(OH)₂) followed by treatment with ether (pp. 783 - 784, "Action of Heat and of Hydrolytic Agents on Gingerol. Formation of Aliphatic Aldehydes (mainly n- Heptaldehyde) and a Ketone, "Zingerone."). Lapworth noted that zingerone dissolved freely in dilute aqueous sodium or potassium hydroxide, and reprecipitated by carbon dioxide. (pp. 785, para. 3).
Connell confirmed the isolation of zingerone by hydrolyzing gingerol with hot aqueous barium hydroxide solution at 64°C. (pp.1034, ln 3 after the structures). In the Experimental section of Connell, hydrolysis of [6]-gingerol was refluxed with barium hydroxide for 1 hr. The aqueous residue from steam distillation was neutralized and extracted with ether to yield zingerone. (pp. 1041, (f) Hydrolysis).
Nomura isolated zingerone by extracting ginger with ether as follows:
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(pp. 770 – 771).
Because each of the references teach methods for extracting zingerone from ginger or a ginger extract (gingerol) , it would have been obvious to one skilled in the art before the effective filing date of the instantly claimed invention, to substitute Ba(OH)2 alkaline solution of Lapworth or Connell with other Group IA or IIA solvent, such as Ca(OH)2 or K(OH). Motivation for such a substitution can be found in the teachings of Lapworth and Nomura. Lapworth discloses the isolation of various constituent components of ginger by extracting ginger with aqueous alcohol solutions, treatment with "milk of lime" (i.e. saturated Ca(OH)₂ solution). Also, Lapworth noted that zingerone dissolved freely in dilute aqueous sodium or potassium hydroxide, and reprecipitated by carbon dioxide. (pp. 785, para. 3). Nomura isolated zingerone from dry powder ginger with sodium hydroxide solution.
Therefore, the claims would have been obvious because the substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (U.S. 2007).
Regarding supercritical fluid extraction, one of ordinary skill in the art before the effective filing date of the instantly clamed invention had knowledge of this method of isolating organic compounds from aqueous solutions and plant specimens. These limitations are deemed to be obvious absent a showing of unexpected results.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35USC 103(a). From the teachings of the references, 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 made, as evidenced by the references, especially in the absence of evidence to the contrary.
Art Made of Record
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. US 1,263,792 (Nomura) (Method of preparing zingiberone).
Conclusion
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/YATE' K CUTLIFF/Primary Examiner, Art Unit 1692
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