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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/28/2025 has been entered.
Status of the Claims
Claims 1-11 and 14-21 are pending, wherein Claim 21 is newly added. Claims 1-10 are withdrawn. Therefore, Claims 11 and 14-21 are presented for examination
Election/Restriction
Applicant elected without traverse Invention II (method for treating morning sickness) and a dosage form comprising Vitamin B-9 as the specific folic acid, and 6-gingerol as the specific gingerol in the reply filed on April 20, 2024. Claims 11 and 13-20 read on the elected species.
Prosecution on the merits will be restricted to the claimed species if no generic claim is finally held to be allowable.
Priority
This application is a 371 national stage application of PCT/US2019/064744 filed on December 05, 2019.
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 obj4ective evidence present in the application indicating obviousness or nonobviousness.
A. New Rejection necessitated by amendment - Claims 11 and 13-20 are rejected under 35 U.S.C. 103 as being unpatentable over Fazylov (WO 2015/080623 A1) (pub. June 2015; effect. filed November 2014) as evidenced by English translation of WO2015/080623 A1 (pub. June 2024) in view of Roy et al. (Ind. Eng. Chem. Res. 1996, 35, 607-612) (pub. 1996) and Perrin et al. (US 2013/0011377 A1) (pub. January 2013; effectively filed July 2011).
Claimed invention
Claim 11 is drawn to a method of treating morning sickness in pregnant women comprising administering a dosage form comprising:
an effective amount of a folic acid selected from a group of natural and synthetic forms of Vitamin B-9,
an effective amount of a gingerol composition to suppress nausea and/or gastric distress,
wherein the gingerol composition comprises one or more gingerol compounds selected from the group consisting of 6-gingerol, 8-gingerol, 10-gingerol, 12-gingerol, 6-shogaol, 8-shogaol, and 10-shogaol,
wherein said gingerol composition is produced under supercritical, near-critical or critical carbon dioxide conditions, and
an oil base, wherein the folic acid is dispersed as a solid suspension in said oil base and the gingerol composition is dissolved in said oil base, wherein said oil base is held in a gel cap.
Prior art
Fazylov teaches a method for preparing tableted vitamin complexes for the prevention of nausea and vomiting during pregnancy. See English translation, e.g., paragraphs [0001]-[0002]. Fazylov teach that vitamins help reduce the intensity of unpleasant manifestations of early pregnancy such as nausea and vomiting. See, e.g., paragraph [0004]. Fazylov teaches that the composition of the prepared tablets comprise folic acid and ginger. See, e.g., paragraphs [0010], [0011] and [0013]. Ginger is obtained from crushed dried roots (rhizomes) of cultivated ginger Zingiber Officinale and concentrated and dried in a vacuum spray dryer. See, e.g., paragraph [0042]. Fazylov also teaches that “gingerol” is an active substance in ginger and contains the resins “gingerol, zingerol, paradol, shogaol, etc.” and improves digestion and metabolism. See, e.g., paragraphs [0042]-[0043]. Folic acid, also known as folacin or Vitamin B9, is essential for fetal development and “[d]uring gestation, folate-dependent processes include growth of the fetus, uterus, placenta and mammary glands, as well as an increase in the number of red blood cells…Thus, during pregnancy the need for this vitamins increases sharply”. See, e.g., paragraph [0045]. Fazylov further teaches that folic acid, vitamin B6, a pharmacologically acceptable source of calcium, dry extract of ginger roots and other adjuvants/excipients are mixed in dry form and mixed with a binder in the form of a solution. The mixture is subjected to wet granulation, dried and sieved in order to obtain the resulting dry granules. See, e.g., paragraphs [0049]-[0050]. The product can be prepared in the form of a solid dosage form such as granules, tablets, and capsules. See, e.g., paragraph [0040]. In Example 4, Fazylov teaches a method to prepare granules comprising said 0.7 mg of folic acid, 20 mg of Vitamin B6, 40 mg of dry ginger root extract, 200 mg of calcium and other additional excipients. The granules containing a dusting agent are used to fill hard gelatin capsules. The capsules were tested on subjects and “showed excellent tolerability and a significant improvement in well-being with nausea, and elimination of gag reflexes”. See, e.g., paragraphs [0087]-[0098].
The method as taught by Fazylov reads on the instant claims as presented below:
Claim 11, directed to a method of treating morning sickness comprising administering a dosage form comprising an effective amount of a folic acid with an effective amount of a gingerol composition to suppress nausea and/or gastric distress. The instant specification defines the phrase “morning sickness” as a condition in which pregnant women experience nausea especially in the first trimester of pregnancy. See, paragraph [0004]. The specification also defines that the extract of the ginger rhizome, Zingiber Officinale, is “associated with one or more of the following 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol.” See, Specification, paragraphs [0025] and [0051]. Fazylov teaches that the composition of the prepared tablets comprises folic acid and the extract of cultivated ginger Zingiber Officinale, which comprises resins “gingerol, zingerol, paradol, and shogaol”. See, e.g., paragraphs [0011]-[0025] and [0042]-[0043]. Thus, the extract encompasses 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol. Fazylov teaches a method for preparing tableted vitamin complexes for the prevention of nausea and vomiting during pregnancy.
While Fazylov teaches compositions containing a folic acid and a gingerol composition, Fazylov does not teach the method, wherein:
said gingerol composition is produced under supercritical, near-critical or critical carbon dioxide conditions;
said dosage form has an oil base, the folic acid is dispersed as a solid suspension in said oil base and said gingerol composition is dissolved in said oil base, as claimed in claim 11; or
said oil base is held in a gel cap.
According to MPEP §2141(III), one of the rationales in the KSR decision states “(C) Use of known technique to improve similar devices (methods, or products) in the same way”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396.
Regarding 1) gingerol composition produced under supercritical, near-critical or critical carbon dioxide conditions:
Roy et al. reported a process for the supercritical carbon dioxide (sc-CO-2-) extraction of oil from ginger root as a function of solvent flow rate, particle size, temperature, and pressure. See title; p. 607, second column. Supercritical fluid extraction has received increasing attention in a variety of fields due to the following features: (a) supercritical fluids provide high solubility and improved mass-transfer rates; (b) operation can be manipulated by changing the pressure or temperature. Carbon dioxide is used as the supercritical fluid mainly because it is a safe, noncombustible, inexpensive, odor less, colorless, tasteless, nontoxic, and readily available solvent. Its low viscosity enables it to penetrate the matrix to reach the material being extracted, and its low latent heat of evaporation and high volatility mean that it can be easily removed without leaving a solvent residue. By varying the temperature and pressure of the CO2 during extraction, the flavor or odor components can be selectively extracted. See Table 1 for the properties of CO2. See p. 607, 1st column. Ginger is one of the major spices with widespread uses in foods, beverage, and medicine. See p. 607, 1st column.
Thus, Roy et al. teach the preparation of ginger extract using a known technique with high solubility and improved mass-transfer rates that can be manipulated as desired by changing the pressure or temperature. The supercritical CO2 extraction technique is used because it involves implementing CO2 as a known safe, noncombustible, inexpensive, odor less, colorless, tasteless, nontoxic, and readily available solvent. Therefore, a person having ordinary skill in the art would have been motivated to obtain ginger extract using a known supercritical CO2 extraction technique because the technique is known to have high solubility and improved mass-transfer rates that can be manipulated as desired by changing the pressure or temperature. The POSA would have further recognized that the solvent, CO2, a safe, noncombustible, inexpensive, odor less, colorless, tasteless, nontoxic, and readily available. The POSA would have had a reasonable expectation of success that the ginger extract can be obtained with a known technique used to extract components from ginger root for medicinal use.
Regarding 2) said dosage form has an oil base, the folic acid is dispersed as a solid suspension in said oil base and said gingerol composition is dissolved in said oil base, as claimed in claim 11 and 3) said oil base is held in a gel cap:
Perrin et al. teach a method of administering compositions for nutritional supplementation in subjects in physiologically stressful states, such as during pregnancy, lactation, or in need thereof. See, e.g., paragraph [0002]. The compositions would include vitamins that “can be used to supplement the nutritional deficiencies observed in patients throughout physiologically stressful states, which, in certain embodiments of the present invention, include prenatal, pregnant and breast-feeding women”. See, e.g., paragraph [0010]. Perrin et al. teach that patients experiencing nausea may have difficulty swallowing nutritional supplements. Due to the soft and elastic nature, administering gel caps improves the patient compliance since they are easier to swallow. See, e.g., paragraphs [0008]-[0009]. The compositions further include pharmaceutically acceptable carriers, which include “binders, diluents, lubricants, glidants, colorants, emulsifiers, disintegrants, starches, water, oils, alcohols, preservatives, and sugars…"pharmaceutically acceptable carriers" refers to dosage forms such as capsules, caplets, gel-caps used with, for example, the compositions of the present invention… "pharmaceutically acceptable carriers" in gel-caps may be in for example, liquid or oil form. See, e.g., paragraph [0035]. Perrin et al. further teaches that the vitamins include vitamins B9 (folic acid) and B6. See, e.g., paragraphs [0005].
Perrin et al. teach a known technique of preparing and administering gel caps since they improve the patient compliance and much easier to swallow, especially for patients experiencing nausea. Perrin et al. further teach adding an oil base as an additional pharmaceutically acceptable carrier in order to improve the compositions of the gel caps for nutritional supplementations in subjects in physiologically stressful states, such as during pregnancy, lactation, or in need thereof. Additionally, Fazylov teaches that the composition comprising folic acid, dry extract of ginger roots and other adjuvants/excipients are combined in dry form and mixed with a binder in the form of a solution. The mixture is further subjected to wet granulation and the solid dosage form can be prepared in the form of granules, tablets, and capsules. Therefore, a person having ordinary skill in the art would have been motivated to prepare gel caps comprising folic acid and ginger roots, and further include an oil base as an excipient to dissolve or disperse said vitamins. The person of ordinary skill in the art would have had a reasonable expectation of success that the prepared gel caps comprising the oil base will be much easier to swallow for patients suffering from morning sickness.
Regarding Claim 14, Fazylov teaches that ginger is obtained from crushed dried roots (rhizomes) of cultivated ginger Zingiber Officinale. See, e.g., paragraph [0042].
With respect to Claims 15-17, Fazylov teaches that folic acid, vitamin B6, a pharmacologically acceptable source of calcium, dry extract of ginger roots and other adjuvants/excipients are mixed in dry form and mixed with a binder in the form of a solution. The mixture is subjected to wet granulation, dried and sieved in order to obtain the resulting dry granules. See, e.g., paragraphs [0049]-[0050]. The product can be prepared in the form of a solid dosage form such as granules, tablets, and capsules. See, e.g., paragraph [0040]. Thus, the resulting mixture would contain folic acid powder that is wetted by the gingerol composition, and prepared in the form of tablets and capsules.
Regarding Claim 18, Fazylov teaches that folic acid and dry extract of ginger roots are mixed in dry form and mixed with a binder in the form of a solution. See, e.g., paragraph [0049].
Regarding Claim 19, Fazylov teaches Example 4, wherein 700 mcg (0.7 mg x 1000 mcg/1 mg = 700 mcg) of folic acid is present.
With respect to Claim 20, Fazylov teaches ginger extract present at 40 mg. See 0090. This falls within the amount range, i.e., “20-40 mg”, disclosed in the instant specification as effective for the purposes of the invention. See Specification, 0027. Thus, the 40 mg gingerol extract in the Fazylov reference is present in amounts effective to for the invention including effective to promote hematopoiesis.
Response to arguments
Applicant argues that the combination of Fazylov and Perrin fails to teach or suggest (i) an oil-based formulation, (ii) use of a gel capsule, (iii) a gingerol composition produced by supercritical or near-critical CO2 extraction, and (iv) a purportedly nonobvious “partitioning” of folic acid and gingerol within the oil base.
Applicant's arguments have been fully considered but have not been found to be persuasive. Fazylov teaches administering folic acid in combination with ginger extract for the treatment of nausea and vomiting during pregnancy, including delivery in capsule dosage form. Perrin teaches oil-based gel capsules for nutritional supplementation in pregnant patients and expressly teaches that such dosage forms improve swallowability and compliance in patients experiencing nausea. A POSA would have been motivated to combine the gingerol/folic acid-containing composition of Fazylov with the il-based gel capsule delivery system of Perrin, with a reasonable expectation of success, in order to improve patient compliance. Incorporation of the gel capsule limitation into Claim 11, therefore, does not overcome the rejection, as it represents a predictable dosage-form modification taught by the prior art.
Applicant’s conclusory arguments concerning “purposeful partitioning”, stability, absorption pathways, and alleged synergistic effects are unpersuasive. These assertions pertain to unclaimed, intended results rather than claim-limiting structural features and, therefore, are not afforded patentable weight requiring these specific teachings by the prior art. Moreover, Applicant has provided no objective evidence supporting the alleged unexpected synergistic results, as required under MPEP § 716. Finally, the prior art, including Roy et al., teaches the claimed limitation of extracting ginger oil from ginger root using supercritical CO2.
Therefore, the rejection is deemed to still be proper and is, therefore, maintained.
B. New Rejection necessitated by amendment - Claims 21 is rejected under 35 U.S.C. 103 as being unpatentable over Fazylov (2015) as evidenced by English translation of WO2015/080623 A1 (2015) in view of Roy et al. (Ind. Eng. Chem. Res. 1996, 35, 607-612) (pub. 1996) and Perrin (2013), as applied to Claims 11 and 13-20, taken further in view of Shao et al. (“Quantitative analysis of ginger components in commercial products using liquid chromatography with electrochemical array detection.” J Agric Food Chem. 2010 Dec 22;58(24):12608-14. doi: 10.1021/jf1029256. Epub 2010 Nov 23. PMID: 21090746; PMCID: PMC3446752.)
Claimed invention
Claim 21 limits claim 11, wherein the gingerol composition has a ratio of 6-shogaol to 6-gingerol of 0.04 to 0.40.
Prior art
Fazylov teaches administering ginger extract containing gingerols and shogaols, including 6-gingerol and 6-shogaol, for treatment of nausea and vomiting during pregnancy. However, Fazylov does not expressly teach the claimed ratio of between the two agents.
However, Shao recognizes the therapeutic usefulness of ginger extracts for nausea, headaches and colds and teaches conventional ginger extracts, including dries and processed ginger preparations that contain both 6-gingerol and 6-shogaol. See pp. 1-3. For example, Shao discloses quantitative concentrations of both 6-ginger and shogaol in commercially available ginger products, from which one can directly derive 6-shogaol : 6-gingerol ratios between 0.19 and 0.40, which overlap the claimed range of 0.04-0.40:
Sample
6-gingerol (mg/100g)
6-shogaol (mg/100g)
6-shogaol / 6-gingerol (mg/100g)
#5
123.07
35.08
0.285041034
#8
277.51
111
0.399985586
#9
737.4
145.62
0.197477624
#10
554.87
115.67
0.208463244
#11
772.33
149.54
0.193621897
See Table 4 at p. 17.
A person of ordinary skill in the art (POSA) would have found it obvious to obtain a gingerol composition having a 6-shogaol : 6-gingerol ratio of 0.04 to 0.40 because Fazylov teaches administering ginger extracts for the treatment of nausea and pregnancy that contain both gingerols and shogaols, including 6-gingerol and 6-shogaol, while Shao teaches that the relative amounts of 6-gingerol and 6-shigaol in ginger extracts vary depending on known processing and extraction conditions that are provided in already known and commercially available ginger products that may be useful for nausea and headaches. The POSA would have had a reasonable expectation that a ginger extract having the makeup of either one of the ginger extract products of Shao (e.g., #5, #8, #9, #10, #11, etc.) can be used to provide ginger extract for treating nausea. The POSA would have found it obvious that controlling or selecting the relative proportions of known active ginger constituents would occur through routine selection of already known extraction methods including those used for commercially available ginger extract products.
Response to arguments
Applicant argues that the claimed ratio is not taught or suggested by the prior art and the ratio is tied to the use of super critical CO2 extraction, which allegedly produces a composition that is chemically and pharmacologically distinct from the extracts of Fazylov.
Applicant's arguments have been fully considered but have not been found to be persuasive. Fazylov teaches administering ginger extract for nausea. While Fazylov does not quantify ratios of constituents, Shao teaches conventional ginger extracts contain claimed ratios of 6-gingerol and 6-shogaol. Thus, the prior art as a whole suggests ginger extracts having the relative ratios of the constituents as outlined in the rejection.
Applicant’s reliance on the extraction method is unpersuasive. Claim 21 is directed to a method for treating a subject comprising administering a folic acid/ginger-containing composition, and does not exclude ginger extracts prepared in a manner different from the product-by-process recited in the claim. Regarding the process of preparation describing the gingerol composition, according to MPEP § 2111.04, such limitations must be given little patentable weight unless they result in a material structural distinction. Applicant has not persuasively demonstrated that the ginger extract product prepared by the claimed process results in a material structural distinction when compared to the ginger extract of the prior art.
Conclusion
No claims are allowed.
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/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622