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 .
DETAILED ACTION
Claims 1-14 as filed September 19, 2024 are under consideration.
The instant application is a divisional (DIV) of Application No. 17/264,152 filed August 24, 2021 (now U.S. Patent No. 12,390,503), which is a 371 of PCT/CN2018/105256 filed September 12, 2018.
Claim Objections
Claims 1-10 and 12-14 are objected to because of the following informalities:
Claim 1: “a loading weight” is properly “the loading weight” because antecedent basis is implicit.
Claims 1-10: spaces should be inserted between the values and the units thereof, e.g., “0.2g” should recite “0.2 g” or “200 mg” in view of the subsequent recitations in mg.
Claims 1, 3, 6, 7, 9: “a content” is properly “the content”.
Claim 1: a residual content” is properly “the residual content”.
Claims 3, 6, 7: “a total content” is properly “the total content”.
Claim 9: “a chromatographic peak area ratio” is properly “the chromatographic peak area ratio”.
Claims 12-14: “FIG. 1” should reference “the figure” or “the drawing” consistent with the amendments to the specification filed November 14, 2024.
Appropriate correction is required.
Claims 13 and 14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 17/264,152.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-6 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Marechal et al. (US 7,569,236, published August 4, 2009) as evidenced by Hu et al. (CN 102138944 A, as evidenced by the Google translation) in view of Bilgic (WO 2012/026904 A1, published March 1, 2012; and Wu et al. (CN 105259268 A, published January 20, 2016, as evidenced by the Google translation).
Marechal teaches drug formulations comprising microgranules containing Gingko Biloba extract (title; abstract; claims). The granules comprise at least one excipient (claim 1). The granules are prepared by process comprising the step of applying a mixture the extract and the excipient over a neutral core (claim 22). The exemplary granules are encapsulated in capsules, each containing 120 mg extract (Example 3, column 8, lines 15-17). The exemplary granules are characterized by a peak area ratio of quercetin to kaemferol (kaempferide) between 0.8 and 1.5 (Table 6), as required by instant claim 9. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). "[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). See MPEP 2144.05.
The extract comprises up to 40 wt% flavonoids and up to 10 wt% terpenes (ketone esters as evidenced by Hu (e.g., page 2, 1st full paragraph, “the main components of ginkgo ketone esters, ginkgo flavonoids and ginkgolides,”)) (claims 5, 6). Flavonoids or flavone glycosides include quercetin, kaemferol and isorhamnetin and terpenes include bilobadide, ginkgolide A, ginkgolide B, ginkgolide C and ginkgolide J (column 1, lines 21-24), as required by instant claims 2-6, 9-11. Regarding the content of rutin of less than or equal to 1.60 mg / 200 mg capsule as required by instant claim 1, Marechal does not specifically teach the content of rutin (flavonoid) which may be broadly and reasonably interpreted as reading on 0 wt% or 0 mg. Regarding the content of biflavonoids of less than or equal to 0.008 mg / 200 mg capsule as required by instant claim 1, Marechal does not specifically teach the content of biflavonoids (flavonoids) which may be broadly and reasonably interpreted as reading on o wt% or 0 mg. Regarding the content of content of genistin (glycoside form of the isoflavone genistein) of 0 as required by instant claim 1, Marechal does not specifically teach the content of genistin which may be broadly and reasonably interpreted as reading on 0 wt% or 0 mg. Regarding the content of content of ginkgolide M of 0 as required by instant claim 1, Marechal does not specifically teach the content of ginkgolide M which may be broadly and reasonably interpreted as reading on 0 wt% or 0 mg.
The extract may be a solid obtained from dried plant raw materials (column 2, lines 18-21). Dry extracts are prepared by evaporation of the solvent such as ethanol (column 2, lines 22-38). Regarding the content of ethanol of less than or equal to 0.2 mg / 200 mg capsule as required by instant claim 1, Marechal does not specifically teach the residual ethanol / solvent content, however, it would have been prima facie obvious to optimize / minimize the residual ethanol / solvent because Marechal expressly teaches removal of solvents inclusive of ethanol and because Marechal expressly teaches the preparations are adjusted so as to mee the requirements of content of solvents (e.g., column 2, lines 25-27).
Marechal does not specifically teach 200 mg capsules and does not specifically teach rutin (flavonoid), biflavonoids (flavonoids), and genistin (glycoside form of the isoflavone genistein) as required by claim 1.
Marechal does not teach fingerprint peaks for rutin, quercetin, kaempferide and isorhamnetin as required by claim 12.
These deficiencies are made up for in the teachings of Bilgic and Wu.
Bilgic teaches dosage forms comprising ginkgo biloba extract (title; abstract; claims). Ginkgo biloba extract comprises terpene, flavone glycoside and less than 5 ppm ginkgolic acid (paragraph bridging page 1 and 2). The amount of ginkgo biloba extract is 1 to 1000 mg, preferably 10 to 200 mg (claim 7; page 2, 2nd full paragraph). Dosages include capsules (claims 12, 13). The dosages are produced by granulation (claim 29).
Wu teaches a fingerprint chromatogram of ginkgo biloba extract useful for quality control (title; abstract; claims). The extract comprises flavonol glycosides inclusive of rutin (page 4, 11th full paragraph; Table at pages 5-6 of original document) and bisflavones (biflavonoids) inclusive of bilobetin and ginkegetin (page 4, 16th full paragraph; Table at pages 5-6 of original document). Reference substance (fingerprint peaks) include any of the substance included in Table 1 inclusive of quercetin, kaempferol, isorhamnetin and rutin (page 5, 6th - 9th full paragraphs; Figures of original document). Wu does not teach genistin.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the ginkgo biloba formulations of Marechal comprising granules encapsulated in capsules to comprise 1 to 1000 mg ginkgo biloba as taught by Bilgic because this dosage is suitable for ginkgo biloba.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the ginkgo biloba of the formulations of Marechal in view of Bilgic to comprise flavonol glycosides inclusive of rutin as taught by Wu in amounts up to 40 wt% as taught by Marechal because Marechal embraces this amount of flavonoids, to comprise bisflavones inclusive of bilobetin and ginkegetin as taught by Wu in amounts up to 40 wt% as taught by Marechal because Marechal embraces this amount of flavonoids, and to be free of genistein because Marechal does not disclose ginkgo biloba to comprise genistein.
Regarding claim 12, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to characterize the ginkgo biloba of the formulations of Marechal in view of Bilgic and Wu according to a fingerprint chromatogram as taught by Wu employing references substances inclusive of quercetin, kaempferol, isorhamnetin and rutin in order to control the quality of the formulations.
Claims 7-11 rejected under 35 U.S.C. 103 as being unpatentable over Marechal et al. (US 7,569,236, published August 4, 2009) as evidenced by Hu et al. (CN 102138944 A, as evidenced by the Google translation) in view of Bilgic (WO 2012/026904 A1, published March 1, 2012; and Wu et al. (CN 105259268 A, published January 20, 2016, as evidenced by the Google translation) as applied to claims 1-6 and 12 above, and further in view of Wang et al. (CN 102078341 A, printed June 1, 2011, as evidenced by the Google translation).
The teachings of Marechal, Hu and Bilgic have been described supra.
Marechal teaches an extract comprising up to 40 wt% flavonoids or flavone glycosides inclusive of quercetin, kaemferol and isorhamnetin (claims 5, 6; column 1, lines 21-24), as required by instant claims 9-11. Marechal teaches a peak area ratio of quercetin to kaemferol between 0.8 and 1.5 (Table 6), as required by instant claim 9.
They do not teach less than 2, less than 1 microgram ginkgolic acids / 200 mg capsule as required by claims 7, 8.
They do not teach a chromatographic peak area of isorhamnetin to quercetin greater than 0.15 as required by claim 9.
These deficiencies are made up for in the teachings of Wang.
Wang teaches a high purity ginkgo flavone having a peak ratio of quercetin to kaempferol of 0.8 to 1.2, a peak ratio of isorhamnetin to quercetin greater than or equal to 0.15, and a concentration of ginkgoic acid smaller than 5 ppm (0.0005 wt%) (title; abstract; claims), as required by instant claims 7-9.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the ginkgo biloba of the formulations of Marechal in view of Bilgic and Wu to have a peak ratio of quercetin to kaempferol of 0.8 to 1.2, a peak ratio of isorhamnetin to quercetin greater than or equal to 0.15, and a concentration of ginkgoic acid smaller than 5 ppm as taught by Wang because these are indicia of high purity. There would be a reasonable expectation of success because the peak area of Wang is consistent with that of Marechal and because the ginkgo biloba of Marechal need not comprise acids.
Allowable Subject Matter
Claims 13 and 14 are free of the prior art. While ginkgo biloba fingerprint spectra are known to the prior art (e.g., Wu et al. (CN 105259268 A)), search and examination did not reveal the HPLC elution spectra of the drawing as required by claim 14 and did not reveal an HPLC elution spectra with at least 90% similarity (calculated and compared as described in paragraphs [0034] and [00194] of the instant specification) as required by claim 13.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Xiao et al. (CN 107915742 A, as evidenced by the Google translation) teaches a ginkgo extract comprising the diterpenoid lactones ginkgolide A, ginkgolide B and ginkgolide K, comprising less than 2 ppm ginkgo acid, and comprising no bilobalide; ginkgo diterpene lactones are unique and have strong specific inhibitory activity on receptors (title; abstract; claims; page 2, 2nd full paragraph).
Castelli et al. (WO 98/17295) teaches ginkgo biloba extracts substantially lacking ginkgolic acid, biflavonoids or free aglycones (title; abstract; claims; page 5, lines 10-32).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISSA PROSSER whose telephone number is (571)272-5164. The examiner can normally be reached M - Th, 10 am - 6 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, DAVID BLANCHARD can be reached on (571)272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALISSA PROSSER/
Examiner, Art Unit 1619
/BENNETT M CELSA/Primary Examiner, Art Unit 1600
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