DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Preliminary Amendments and Remarks, filed 6 March 2024, in the matter of Application N° 18/516,509. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-13 have been canceled. Claims 14-34 have been added and are supported by the originally-filed disclosure.
No further amendments have been made.
No new matter has been added.
Thus, claims 14-34 now represent all claims currently under consideration.
Information Disclosure Statement
One Information Disclosure Statement (IDS) filed 21 November 2023 is acknowledged and has been considered.
Specification - Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Claim Rejections - 35 USC §102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 14, 16, 21, and 23 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Yamaguchi et al. (USPN 11,110,109 B2).
The limitations recited by instant claim 16 are directed to a solid co-amorphous (i.e., non-crystalline) composition comprising a flavonoid and an amino acid.
Claim 16 limits the flavonoid to rutin and limits the amino acid to arginine. The molar ratio of rutin to arginine ranges from 1:1 to 1:4.
The claims additionally recite “and solvates thereof.” However, the solvate, which is defined by the instant specification as being either water or ethanol, is broadly and reasonably considered as being absent from the recited composition, particularly since the composition is recited as being a solid (i.e., devoid of liquid).
Mixtures 1-05, 1-06, and 1-07 presented in Table 4 disclose rutin:arginine compositions that meet the recited limitations and molar ratios (see col. 5). The practiced compositions are further disclosed as presented as an oral composition such as a food product, a dietary supplement, etc. (see claim 7), further defined as being in such solid dosage forms as a pill, tablet, or capsule (see claims 8 and 9).
The reference is thus considered to teach each of the instantly claimed limitations.
Claims 14 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hatwar et al. (JDDST; 2021; of record).
The limitations of the claims are discussed above.
Hatwar discloses spheronized pellets comprising a co-amorphous mixture of quercetin and arginine (see e.g., Abstract). The pellets are then fed to rats (see pg. 3, section 2.9.2.).
The reference thus expressly meeting the limitations of the claims.
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 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. Applicants are 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 14-34 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (US Pre-Grant Publication Nº 2009/0082400 A1) in view of Gouveia et al. (Intl. J Mol. Sci.; published 28 July 2022).
The limitations of claims 14, 16, 21, and 23 are discussed above.
The limitations of claims 15 and 17-20 recite different combinations of flavonoids and arginine or lysine as the amino acid, and in different ratio ranges. Claims 22 and 24-27 each recite the same compositional limitations as claim 21, but recite including the composition of claims 22, and 24-27, respectively. Claims 28-34 each recite the same method treating metabolic syndrome or improving intestinal microbiota comprising administering the composition recited by claims 14-20, respectively.
Lee discloses a pharmaceutical composition comprising a pyrone analog such as a flavonoid, a cyclodextrin, and a basic amino acid. The amino acid is taught as being arginine or lysine (see e.g., claims 181-182). Claim 185 discloses that the pyrone analog is selected from quercetin and fisetin. Claim 199 discloses a method of making a solution for the composition comprising mixing a pyrone analog such as a flavonoid, and a basic amino acid.
Other flavonoids disclosed by Lee include: rutin, genistein, naringenin, and apigenin. See ¶[0024], ¶[0028], ¶[0036], ¶[0371], and ¶[0372].
Regarding the amount of flavonoid, ¶[0352], ¶[0371], and ¶[0372] each disclose that the amount of flavonoid is present in a concentration greater than 0.5 mM, 1 mM, 5 mM, 10 mM, 20 mM, 30 mM, 33 mM, 40 mM, 50 mM, 60 mM, 70 mM, 80 mM or greater than 80 mM.
Regarding the amount of amino acid (e.g., arginine or lysine) that is used, ¶[0359] discloses that arginine will be present in a concentration between 50-90 mM, between 60-80 mM, and in some cases, present at a concentration of about 70 mM. Similarly, lysine will be present in a concentration between 50-80 mM, between 60-70 mM, and in some cases, present at a concentration of about 65 mM.
Thus, the limitations of claim 15 are met since a concentration of 10 mM or 20 mM of quercetin or fisetin and a concentration of 60 mM or 90 mM of arginine would produce the recited range of 1:3 (i.e., 20 mM: 60 mM) to 1:9 (i.e., 10 mM: 90 mM).
The limitations of claim 16 are met since a concentration of 20 mM or 60 mM of rutin and a concentration of 60 mM or 80 mM of arginine would produce the recited range of 1:1 (i.e., 60 mM: 60 mM) to 1:4 (i.e., 20 mM: 80 mM).
The limitations of claim 17 are met since a concentration of 5 mM or 20 mM of genistein and a concentration of 50 mM or 60 mM of arginine would produce the recited range of 1:3 (i.e., 20 mM: 60 mM) to 1:10 (i.e., 5 mM: 50 mM).
The limitations of claim 18 are met since a concentration of 20 mM of naringenin and a concentration of 60 mM of arginine would produce the recited ratio of 1:3 (i.e., 20 mM: 60 mM).
The limitations of claim 19 are met since a concentration of 10 mM or 20 mM of apigenin and a concentration of 60 mM or 80 mM of arginine would produce the recited range of 1:3 (i.e., 20 mM: 60 mM) to 1:8 (i.e., 10 mM: 80 mM).
The limitations of claim 20 are met since a concentration of 20 mM of rutin or naringenin and a concentration of 60 mM of lysine would produce the recited ratio of 1:3 (i.e., 20 mM: 60 mM).
The limitations of claims 21-27 are met by claims 91-93 and claims 181-185 whereby the more generic compositions are disclosed as being in the form of a pharmaceutical composition. Claim 93 discloses that the formulation is for oral administration. Paragraph [0544] discloses that such oral formulations may be in the form of tablets, capsules, and granules.
The reference does disclose administering the practiced compositions to an animal (e.g., human) for the purposes of decreasing a side effect in said animal (see e.g., claims 129 and 134; and ¶[0079]-¶[0080]). Paragraph [0079] elaborates on the method of treatment and indicates that a side effect to be treated is a decrease in tissue metabolic function.
Based on this disclosure, the skilled artisan would have an expectation that compositions possessing flavonoids and amino acids help to increase metabolic function in those to whom it is administered.
This position is additionally supported by such disclosures as provided by Gouveia which publishes a study on the effects of the treatment with flavonoids on metabolic syndrome (see e.g., Title; Abstract). The Abstract highlights that “[d]iets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS)” and that “[p]olyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa.” “The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose.”
Figure 1 of the reference identifies the following flavanone, flavone, flavanol, and isoflavones as being derived from polyphenols:
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The article concludes stating that the “review offers evidence in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and consequently reduce[s] the risk of diseases associated with MetS. Except for BW [body weight] and BMI [body mass index], all other parameters were significantly influenced by flavonoids.”
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the recited method of treatment.
Summarily, the foregoing teachings of Lee establish that solid, oral formulations comprising the flavonoids as claimed and amino acids, such as arginine and lysine, are known to be administered to animals (i.e., humans) for the treatment and mitigation of metabolic side effects. While Lee does not expressly disclose treating metabolic syndrome or improvement of intestinal microbiota, Gouveia does and directly credits the consumption of flavonoids and related flavonoid compounds with accomplishing this. Applicants are directed to MPEP 2112.01(I) which states that “[w]here the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established” and MPEP 2112.02(I) which states that “if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art device. When the prior art device is the same as a device described in the specification for carrying out the claimed method, it can be assumed the device will inherently perform the claimed process.” Gouveia serves as evidence to both of the foregoing points.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
All claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615