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 .
Priority
The instant application is a national stage entry of PCT/US2022/023497 filed on 4/05/2022, which claims priority benefit of U.S. Provisional Application No. 63/172297 filed on 4/08/2021 under 35 U.S.C. 119(e).
Information Disclosure Statement
The information disclosure statement (IDSs) submitted on 3/25/2024, 2/12/2025, 3/21/2025, 6/11/2025, 7/11/2025, and 1/16/2026 are in compliance with the provisions of 37 C.F.R. 1.97. Accordingly, all references cited in these IDSs have been fully considered.
However, the listing of references in the specification (page 32) is not a proper IDS. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." So unless the references have been cited by examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because of the following informalities: incorrect spelling and improper recitation of scientific names (the genus names are not capitalized). To resolve these informalities, the terms “bacillus subtillis”, “trichoderma”, and “aspergillus terrus” in the second paragraph of page 28 should be amended to “Bacillus subtilis”, “Trichoderma”, and “Aspergillus terreus”, respectively.
In addition, the use of the terms “GE”, XK”, and “HiPrep”, which are trade names or trademarks used in commerce, has been noted in this application (last par., page 27; first par., page 28). These terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 5-14, 18-25, and 32-43 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. In this case, claims 4, 17, and 31 are multiple dependent claims from which claims 5-14, 18-25, and 32-43 depend. Thus in accordance with MPEP § 608.01(n)(I)(F), claims 5-14, 18-25, and 32-43 have not been further treated on the merits with regards to the application of prior art.
Claim 30 is objected to because of the following informalities: incorrect placement of commas (the first comma in lines 2 and 4 should be moved immediately after “mono-” in lines 1 and 3). Appropriate correction is required.
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 4, 14, 18, 26, 32, 36, and 43 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The term “about” is a relative term which renders the claims indefinite because it is confusing what values are allowed. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For example, does “about 1 mM to about 30 mM” in claim 4 encompasses up to -/+1 mM of the recited concentration, or is it limited to -/+0.1 mM? Similarly, does “about 4 to about 6” in claim 14 includes up to -/+0.2 of the recited pH value, or is it restricted to -/+0.1?
For the purpose of applying prior art, claims 4, 14, 18, 26, 32, 36, and 43 are treated as if the relative term “about” is absent.
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.
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 1-4, 15-17, 27-28, and 31 are rejected under 35 U.S.C. 103 as being obvious over Schmidt-Dannert et al. (US 2005/0208643 A1) in view of Sun et al. (Frontiers in Plant Science 2016, Vol. 7, Article 410, pages 1-14).
Schmidt-Dannert et al. discloses methods for producing flavonoids and other organic compounds using polypeptides or host cells (Abstract), wherein the produced flavonoids include anthocyanins (par. [0007], [0054]; Figure 28).
Examples of polypeptides that can be used in the disclosed methods are those having the enzymatic activity of UDP-glucose:flavonoid 3-O-glycosyltransferase and UDP-glucose:flavonoid 5-O-glycosyltransferase (Table 1, page 7). The polypeptides used are substantially pure or were subjected to purification techniques, and can also be immobilized on a substrate (par. [0091]-[0095]).
The production methods can be performed within a cell or outside a cell such as in a container or column (par. [0073]). In other words, a substantially pure polypeptide or a cell-free extract containing a substantially pure polypeptide can be used to produce any flavonoid (par. [0113]-[0114]). Once produced, the flavonoid can be isolated using common isolation procedures like extraction, distillation, and ion-exchange (par. [0117]).
Schmidt-Dannert et al.’s methods are comparable to the instant application’s methods for the following reasons:
Regarding claims 1, 15, and 27: producing a flavonoid like an anthocyanin from an anthocyanidin, also known as 3-OH anthocyanin (Figure 28) is the same as “A method of producing an anthocyanin from an anthocyanidin”.
Treating an anthocyanidin with a substantially pure polypeptide having UDP-glucose:flavonoid 3-O-glycosyltransferase or UDP-glucose:flavonoid 5-O-glycosyltransferasethe enzymatic activity, or a cell-free extract containing said polypeptide in a container, is analogous to the step “a) adding to a mixture comprising… (i) an anthocyanidin of Formula I” (claim 1) or “Formula Ia” (claim 27)… and (iii) a glycosyltransferase enzyme to form a reaction mixture”, as well as “a) in a cell-free vessel, providing a glycosyltransferase enzyme; b) adding an anthocyanidin… to the cell-free vessel to form the anthocyanin” (claim 15).
Isolating the produced flavonoid like an anthocyanin using common isolation techniques such as extraction, distillation, and ion-exchange corresponds to the step “c) isolating the anthocyanin” (claims 1 and 27) and “c) removing the anthocyanin from the cell-free vessel” (claim 15).
Schmidt-Dannert et al. is different from the instant claims in that it does not teach the structure of anthocyanidin, mixing the anthocyanidin with “(ii) a glycosylated uridine-5’-diphosphate of Formula II” (claims 1 and 27) or “a glycosylated uridine diphosphate” (claim 15) in a “suitable solvent”, and the step “b) removing the supernatant from the reaction mixture from (a)” (claims 1 and 27).
Enzymatic synthesis of an anthocyanin from an anthocyanidin having the structure of Formula I/Ia utilizing a glycosyltransferase, however, is known in the art. For example, Sun et al. teaches expressing a recombinant form of a flavonoid 3-O-glycosyltransferase from Freesia hybrida (Fh3GT1) in Escherichia coli and purifying it (second par. in right col., page 4). Sun et al. characterizes Fh3FT1 by mixing the purified enzyme or extracts comprising the enzyme with flavonoid substrates (ex. cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin) and 10 mM UDP-glucose/UDP-galactose in phosphate buffer at 30°C, centrifuging the mixtures, and collecting the supernatants (third par. in right col., page 4; first three par. in left col., page 5). Results show that Fh3GT1 catalyzes the transfer of glucose/galactose from the sugar donor (i.e., UDP-glucose/UDP-galactose) to the anthocyanidin at the 3-position, thereby forming anthocyanins such as cyanidin 3-O-glucoside (Figure 4, page 8; Table 1, page 9).
Based on the teachings of Sun et al., a person with ordinary skill in the art before the effective filing date of the claimed invention to perform Schmidt-Dannert et al.’s methods by adding 10 mM UDP-glucose/UDP-galactose to a flavonoid 3-O-glycosyltransferase like Fh3GT1 and an anthocyanidin like cyanidin (which satisfies the structure of Formula I/Ia) in a phosphate buffer and removing the supernatant prior to product isolation. It can be expected that combining the teachings of Schmidt-Dannert et al. and Sun et al. would successfully produce an anthocyanin like cyanidin 3-O-glucoside because the UDP-glucose/UDP-galactose would serve as the glucose/galactose donor. Obviousness is based on the rationale that all claimed elements were known in the prior art and their combination would have yielded nothing more than predictable results. See MPEP § 2143 and KSR, 550 U.S. 398, 82 USPQ2d at 1395.
Claims 1, 15, and 27 are thus obvious over Schmidt-Dannert et al. in view of Sun et al..
Regarding claims 2, 16, and 28: Sun et al. shows that Fh3GT1 catalyzes the transfer of glucose/galactose to flavonoid substrates such as cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin, which meets the limitations “the anthocyanidin of Formula I comprises a member of the group consisting of cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin”, “the anthocyanidin is a member of the group consisting of cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin”, and “the anthocyanidin of Formula Ia is a member of the group consisting of cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin, a glycosylated cyanidin, a glycosylated delphinidin, a glycosylated malvidin, a glycosylated pelargonidin, and a glycosylated peonidin”, respectively.
Regarding claims 3, 17, and 31: the UDP-glucose/UDP-galactose satisfies “G in Formula II comprises a member of the group consisting of glucose, galactose, xylose, arabinose, and rhamnose”,
Regarding claim 4: the UDP-glucose/UDP-galactose being used in the amount of 10 mM fulfills “the glycosylated uridine-5'-diphosphate of Formula II has a concentration in the reaction mixture of about 1 mM to about 30 mM”.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE F PAGUIO FRISING whose telephone number is (571)272-6224. The examiner can normally be reached Monday-Friday, 8:00 a.m. - 4:00 p.m..
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, Melenie L. Gordon can be reached at (571) 272-8037. 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.
/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651