DETAILED ACTION
Status of Claims
New claims 20-28 were added. Claims 20-26 which belong to previously examined group I, claims 1-14 are being examined in this office action. Claims 27-28 which belong to non-elected group II claims 15-18 which were previously withdrawn are hereby withdrawn as being directed to a non-elected invention at this time. Thus, the claims under examination in the current office action are claims 1-14, 20-26.
Claim Objections
Claim 1 is objected to because of the following informalities: The claim was amended to recite: a whole liquid pharmaceutical composition and should instead read “the whole liquid pharmaceutical composition” since it is clear from the claim that the kuding saponin is a component of the liquid pharmaceutical set forth in claim 1 and claimed in claim 1, and not a different/additional liquid pharmaceutical composition.
Claim 24 is objected to because of the following informalities: Claim 24 uses additional names for Kudinoside A, etc. but has previously referred to these compounds by Kudinoside A, etc. Please use consistent names for compounds within the claims. E.g. Kudinoside A, Kudinoside D, etc. If applicant’s want to include the IUPAC name then place that name in parentheses after the more commonly known name, e.g. Kudinoside A (3β-12α-19α…).
Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
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) 1-14 and 20-26 is/are rejected under 35 U.S.C. 103 as being unpatentable CN106420852A (‘852), and further in view of CN103893165 and CN104208160, and as evidenced by Tang et al. (J. Nat. Prod., 2005, 68, 1169-1174) and JP6426752.
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1-6, 20-25, ‘852 teaches liquid pharmaceutical compositions comprising aqueous ethanol solutions and therapeutically effective amounts of a kuding saponin compound which is isolated from the same plant species instantly claimed via ethanol extraction, i.e. ilex cornut Lindl., ilex kudincha C. J. Tseng, ilex rotunda Thunb., specifically an inhalation solution or inhalation suspension, which pharmaceutically acceptable carrier comprising water and alcohol/ethanol (See entire document; Background of invention section; Paragraph beginning: “The purpose of this invention is achieved…Selecting raw materials…”; Example 6; The preparation of aerosol-on Kuding tea section; The preparation of Spray-on Kuding tea; abstract). ‘852 does not specifically teach what kuding saponin compound(s) are isolated via their ethanol extraction, but these ethanol extractions, specifically of ilex kudincha C. J. Tseng, clearly include Kudinoside-A (which reads on new claims 20-24 as applicant’s preferred compound KA claimed in claim 24 which contains an oligosaccharide (comprising an arabinose, glucose, and rhamnose in the form of a trisaccharide) is Kudinoside A (As per applicant’s specification), Kudinoside-D, etc. as is evidenced by Tang (See entire document; abstract; pg. 1173, left col. paragraph immediately before Experimental section heading). ‘852 teaches in their paragraph describing the preparation of Aerosol Folium Illicis that they use different amounts of Kuding tea (extract) with 5g of distilled water and 150 g, anhydrous ethanol were prepared to provide from 0.05-5 mg/spray (equivalent to a liquid concentration of 0.5-50 mg/mL) (See entire document; Background of invention section; Paragraph beginning: “The purpose of this invention is achieved…Selecting raw materials…”; Example 6; The preparation of aerosol-on Kuding tea section; The preparation of Spray-on Kuding tea; abstract). The solution was poured into containers at room temperature, the valve was installed and sealed, and then a quantitative amount of HFA-134a was injected using a press-filling machine (See entire document; Background of invention section; Paragraph beginning: “The purpose of this invention is achieved…Selecting raw materials…”; Example 6; The preparation of aerosol-on Kuding tea section; The preparation of Spray-on Kuding tea; abstract).
Regarding claims 1, 7 and 10, and 20-25, ‘852 teaches in their paragraph describing the preparation of Aerosol Kuding Tea that they use different amounts of Kuding tea (extract) with 5g of distilled water and 150 g, anhydrous ethanol were prepared to provide from 0.05-5 mg/spray (equivalent to a liquid concentration of 0.5-50 mg/mL). The solution was poured into containers at room temperature, the valve was installed and sealed, and then a quantitative amount of HFA-134a was injected using a press-filling machine. It would be obvious to optimize the amounts of the Kuding saponin in the Kuding tea of ‘852 to fall within the claimed range of 0.001-0.050% by mass, specifically the now claimed 0.006-0.030% by mass based on the total mass of the liquid pharmaceutical composition as claimed because ‘852 teaches using the same active agents for treating cough and pulmonary diseases (See entire document; Background of invention section; Paragraph beginning: “The purpose of this invention is achieved…Selecting raw materials…”; Example 6; The preparation of aerosol-on Kuding tea section; The preparation of Spray-on Kuding tea; abstract) and as is evidenced by JP6426752 it was known to treat pulmonary diseases, specifically COPD with the Kuding saponins/Kuding teas of ‘852, specifically Kudinosides A, D, etc. (See entire document; paragraph beginning: In order to test the therapeutic effect of a single substance in bitterling tea extract on asthma, two volunteers (51-year-old male, 72-year-old male)…; paragraphs discussion Figures, e.g. fig. 4, fig. 6, fig. 7, fig. 8, etc.; Paragraphs after (Relaxation effect of kudinoside on asthmatic contraction of animals) discussing effects of Kudinosides; Section: paragraph beginning with: In one embodiment, the compounds of formula (I) may be used for the treatment of lung disease. In certain embodiments, the compound of Formula (I) is in a pharmaceutically acceptable carrier. In one embodiment, the disease is a lung disease comprising at least one of asthma, COPD, bronchitis, chronic or acute bronchoconstriction, adult respiratory distress syndrome, acute lung injury and bronchiectasis. In one embodiment, the lung disease may include asthma and COPD. And paragraphs discussing COPD and asthma following; Claims).
Ascertainment of the difference between prior art and the claims
(MPEP 2141.02)
Regarding claims 1-14 and 20-26, ‘852 does not teach wherein the composition comprises a buffer having the claimed pH, specifically the claimed disodium hydrogen phosphate-potassium dihydrogen phosphate buffer of instant claims 8, 13-14, 26, etc. or wherein the composition further comprises the claimed cosolvent and/or stabilizer of instant claim 9, specifically Tween 80 (instant claim 11) and/or disodium edetate (instant claim 12) in the claimed amounts/mass% (claims 11-14). However, these deficiencies in ‘852 (as evidenced by Tang) are addressed by CN103893165 and CN104208160.
CN103893165 teaches formulations/compositions for inhalation for treating lung diseases, specifically asthma and COPD, which comprise the claimed buffer/buffer system comprising disodium hydrogen phosphate-potassium dihydrogen phosphate having a pH of 7.0 (See Examples 3 and 4; technical field section; paragraph beginning: The nebulized inhalant of the present invention may be formed into a medicament vapor, mist or aerosol…).
CN104208160 teaches other aerosol formulations for delivery by breathing/inhalation which comprise aqueous ethanol solutions (300 mL at 0.789 g/mL of ethanol (236.7 g) and 300 ml of water solution at ~1 g/ml containing 0.5% of disodium edetate= 1.5 g of disodium edetate and ~298.5 g of water, which would be about 0.25% by mass/weight of the final mixture (1.5/587.7 g) which is very close to the claimed 0.2 mass% claimed, Tween 80 (10 g, 10/587.7= 1.7% by mass/weight) and 1g butylated hydroxytoluene (Example 7).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art at the time of the instant filing to have included the claimed buffer, specifically the combination of disodium hydrogen phosphate-potassium dihydrogen phosphate having a pH of 7.0, with the claimed cosolvents, solubilizers, e.g. Tween 80 and disodium edetate, into the compositions of ‘852 in order to develop the claimed formulations/compositions because each of the claimed agents was known to be useful for effectively formulating inhalation aerosols for treating lung/pulmonary diseases, specifically asthma and/or COPD. Thus, it would be obvious to combine known effective components for forming inhalation aerosol compositions for treating COPD and asthma in order to form new/effective inhalation aerosol compositions for treating COPD and asthma because, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
It would have been obvious to one of ordinary skill in the art at the time of the instant filing to have optimized the amounts of ethanol, tween-80 and disodium edetate and in the inhalation aerosol formulations taught by the combined prior art in order to form the claimed compositions having the specific components in the instantly claimed amounts because it was known to use ethanol, tween-80 and disodium edetate for forming inhalation/aerosol compositions for effectively delivering active agents by breathing/inhalation, and “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.’" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding the claimed stable limitation, applicants have not defined stable in any specific way, and this stability is a result effective property of forming the claimed composition which is rendered obvious by the prior art as discussed above and as such would result from forming the claimed obvious composition especially since as long as the composition is stable for even the smallest period of time it reads on the instant claim limitation as the claim is currently written.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 USC 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 would have been 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.
Response to Arguments/Remarks
Applicant’s amendments to the claims and specification have overcome the previous objections to the specification and claims and have overcome the previous 112 rejection(s) which are hereby withdrawn. Applicant’s arguments with respect to the double patenting rejections were persuasive and these double patenting rejections are hereby withdrawn. Applicant’s amendments to the claims have prompted the new claim objection and updated grounds of rejection presented herein at this time.
Applicant’s arguments with respect to the 103 rejection have been fully considered but are not persuasive at this time. Firstly, applicant’s argue that the concentrations of ethanol and kuding extract/saponin compounds in the prior art Zhu are much higher than the concentrations instantly claimed. The examiner respectfully points out that Zhu teaches using their liquid formulation to treat similar conditions to those instantly disclosed, e.g. COPD, asthma, etc. and it is known in the art to optimize the amounts of active agents in a medicinal formulation in order to achieve the proper dosage/most effective concentration of active agents in the formulation which are also cost effective. Further, it would have been obvious to optimize the amounts of ethanol in the formulation to the concentration instantly claimed because it is known to limit ethanol in formulations as it has negative effects on humans to which it is administered, e.g. risk of toxicity from ethanol/alcohol effects (CNS depression, etc.). Further, applicants have demonstrated no criticality of their claimed amounts, specifically that other amounts of ethanol or active kuding saponin compounds do not work in their formulations. Additionally, it is also known in the art to use saponins in the claimed amounts in pharmaceutical/medicinal formulations see for instance CA2705573 (see table 1). As such, because it is known to use other saponins in the claimed amounts the examiner maintains that it would be obvious to optimize the amounts of saponin used in the prior art in as discussed above in order to formulate the instantly claimed compositions because it was already known in the art to use aqueous ethanol formulations of the claimed kuding saponins to form medicinal compositions for treating the same conditions instantly disclosed and it is known, “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Applicants then argue that there is no buffer in example 6 of Zhu. The examiner respectfully points out that the instant rejection is an obviousness rejection not an anticipatory/102 rejection and as such Zhu does not need to teach each and every feature in order to render the claims obvious because the rejection is not solely over Zhu, it is instead over the combination of references which is discussed above. Additionally, applicants have not defined stable and as such even a femtosecond of any kind of stability by the compositions of the prior art would read on the claimed stable formulation. If applicant’s composition achieves a specific stability, e.g. over a specific period of time or over specific conditions/temperatures, etc. the examiner suggests that these are limitations that applicants could include into their claim(s) to help to distinguish applicants claims from the prior art. Thus, contrary to applicant’s arguments the examiner maintains that the combination of the reference does still render the instant claimed invention obvious for the reasons discussed above especially in the absence of evidence of criticality of applicant’s ranges, etc. as is discussed above especially since it was known to use the claimed active agents to treat the same lung diseases which are instantly disclosed and it is known, “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Applicants then argue that there is no reason to believe that a skilled artisan would decrease the mass percentage of ethanol in the aerosol of Zhu to the claimed 1-5% of ethanol from the much higher amount of Zhu. The examiner respectfully disagrees again for the reasons which are discussed above which are incorporated herein, especially since it was known to treat the same conditions which are instantly disclosed with aqueous ethanolic solutions of the same kuding saponins and because it is known, “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), especially since as discussed above applicant’s claims do not require any specific stability nor have applicant’s specifically defined stable to mean anything particular in their specification nor is stability defined by a specific period of time for the formulation to remain in solution or not to have evaporated or precipitated, etc. in applicant’s originally filed disclosure.
Applicants then argue that Huang is silent on use of an ethanol is a stable liquid formulation of kuding saponin. The examiner again respectfully points out that applicants have not defined stable and as such even the most fleeting stability reads on the claimed stable limitation and the claimed composition is not required to be in any specific form except a liquid comprising aqueous ethanol in the claimed percentages, i.e. the liquid composition could contain dispersion of particles in the liquid, be in the form of an emulsion, or all the components could be in solution, etc. all of which reads on the instant claims, e.g. claim 1. Additionally, as discussed above the instant rejection is an obviousness rejection not an anticipatory rejection and as such Huang need not teach each and every feature of applicants invention as it is the combination of the references together which render the instant invention(s) obvious at this time.
Applicants then argue that Du also teaches using ethanol in a much higher percentage than instantly claimed and that the active agent in Du is tea tree oil and as such it does not relate to formulations of kuding saponin. The examiner respectfully points out that Du is not used to teach kuding saponin and ethanol compositions beyond showing that it was known to use various amounts of ethanol as needed when formulating liquid natural product compositions for medicinal use, specifically for inhalation use. Du was used to teach the features which are discussed above, specifically that it was known to form aerosol formulations for delivery by breathing/inhalation which comprise aqueous ethanol solutions and which contain 0.5% of disodium edetate= 1.5 g of disodium edetate and ~298.5 g of water, which would be about 0.25% by mass/weight of the final mixture (1.5/587.7 g) which is very close to the claimed 0.2 mass% claimed, Tween 80 (10 g, 10/587.7= 1.7% by mass/weight) and 1g butylated hydroxytoluene (Example 7), and as previously discussed (above) it would have been obvious to optimize the amounts of ethanol in the formulation comprising the claimed kuding saponin because this is something that one of ordinary skill in the art routinely does especially since the prior art already recognizes formulating the claimed kuding saponins in aqueous ethanol for administering the kuding saponin for the same lung conditions instantly disclosed, and this optimization is obvious for one of ordinary skill in the art to accomplish because applicants have not demonstrated any criticality of the claimed amounts of ethanol, kuding saponin, etc., specifically that other amounts do not work to form “stable” formulations, etc. The optimization of the claimed amounts of ethanol, kuding saponin etc. as discussed above remain obvious to one of ordinary skill in the art at this time because “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
The examiner notes that if there is criticality of applicant’s claimed ranges of ethanol, kuding saponin, etc. clarifying these findings of criticality would help to distinguish applicant’s claims from the prior art.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 USC 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 would have been 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.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new/revised ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin E Hirt whose telephone number is (571)270-1077. The examiner can normally be reached 10:30-7:30 ET M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue X Liu can be reached at 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERIN E HIRT/Primary Examiner, Art Unit 1616
Prosecution Insights