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
1. Applicant’s preliminary amendment filed on January 26, 2024 is acknowledged. Claim 3-5, 11, 13, 15, and 18-26 have been amended. Claim 41 has been added. Claims 6-10, 14, 17, and 27-40 have been canceled. Claims 1-5, 11-13, 15-16, 18-26 and 41 are currently pending and under examination.
Priority
2. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on February 20, 2025 and June 3, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. An initialed copy is attached hereto.
Drawings/Specification
4. The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: the drawings dated June 3, 2023 has 18 drawings within; however the specification only addresses seven drawings. Applicant must address all drawings of record. Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
5. Claims 15, 16, and 22-25 are objected to because of the following informalities: said claims depend upon a rejected based claim. 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
6. Claims 1, 26 and 41 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is rendered vague and indefinite by the use of the phrase “characterized in that a medium” in the fourth paragraph of the claim. It is unclear what is meant by said phrase, as there is more than one medium to which this statement can refer. As written, it is impossible to determine the metes and bounds of the claimed invention.
The term “ambient temperature” in claim s 26 and 41 is a relative term which renders the claim indefinite. The term “ambient” 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. The term can vary depending upon different factors such as weather, location as well as heating and cooling in the area.
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.
7. Claim(s) 1-5, 11-13, and 18-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by JP3065348 B2; published: 7/17/2000; google patent translation provided.
Independent claim 1 is drawn to a method of continuously manufacturing microorganisms, comprising: continuously supplying, for 20 hours or longer, a first concentrated partial medium from a first medium storage vessel at constant flow rate Y1 (L/h), a second concentrated partial medium from a second medium storage vessel at flow rate Q (L/h), and water at constant flow rate Y2 (L/h), each independently to a thermostatic vessel, or to the thermostatic vessel after mixing in a mixing vessel or a supply line; growing microorganisms that can assimilate a carbon source and grow in a culture solution in the thermostatic vessel by aerating the thermostatic vessel to continuously manufacture a microorganism culture solution for 20 hours or longer; and continuously discharging the microorganism culture solution comprising a substantially constant concentration of microorganisms from the thermostatic vessel at constant flow rate F (L/h) for 20 hours or longer; characterized in that a medium required for the microorganisms is formed by a first medium component contained in the first concentrated partial medium, a second medium component contained in the second concentrated partial medium, and water.
The present invention developed a continuous fermentation process that maintains high levels of growth and productivity over an extended period of time. Fresh fermentation medium is added and spent fermentation broth is removed without interruption. Preferably, fresh fermentation medium is continuously added to the fermenter, and spent fermentation broth is continuously removed or removed to keep the volume of fermentation broth in the container constant over a period of time (located under summary of the invention header; meets portion of claim 1) maintaining a continuous fermentation of microorganisms in fermented broth, in particular for continuously fermenting heterotrophic microorganisms. The method involves diluting the fermented broth with an effective amount of fresh fermentation medium containing a growth rate limiting amount of a carbon source (meets claim 3). The production phase of the fermentation can be effectively extended. Depending on the type of fermentation, a high cell density can be achieved. In addition, the method involves controlling various fermentation parameters, including temperature and pH, to improve cell growth with the addition of fresh fermentation medium or, preferably, by adding new fermentation medium and maintaining a substantially constant volume of fermented broth by removing spent fermentation broth.
The dilution rate (D) is equal to the volumetric flow rate of fresh fermentation medium into the fermentation vessel and the consumed fermentation broth leaving the vessel divided by the volume of fermentation broth (meets claim 4). Is the reciprocal of time, and for the purposes of the present invention, unless otherwise specified, it is hr -1 . The dilution rate is equal to the number of liquid volumes of the container passing through the container per unit time and is the reciprocal of the average residence time (meets claim 2).
Addition of fresh fermentation medium and removal of spent fermentation broth may be stationary or periodic, but preferably is stationary. The addition of fresh fermentation medium and the removal of spent fermentation broth may or may not be simultaneous, but is preferably simultaneous. (see page 5-6, paragraph below detailed description of the invention; meets claim 1, 20 and 21). Further, the invention encompasses performing the fermentation by diluting the fermented broth with the addition of fresh fermentation medium. A fresh fermentation medium is generally an aqueous solution that contains a growth rate-limiting amount of a carbon source and is added to a fermentation vessel. In particular, the fresh fermentation medium may be water or water with nutrients such as glucose and other substances added to it. It is recognized that with the introduction of a new fermentation medium, the nutrient concentration in the fermentation broth must be maintained at a concentration sufficient to support the growth and/or production of extracellular material. Such nutrients can be added in the fresh fermentation medium or independently. In particular, such nutrients include carbon sources; nitrogen; phosphates; sulfates and magnesium, iron and other trace metals. The rate of addition of the carbon source can be monitored and the carbon source can be supplied at a rate that achieves the desired limited growth rate (meets claim 3). The carbon source is supplied continuously to maintain the desired limited concentration. In particular, maintaining the supply of carbon source, the growth rate of about 25% to U max up to about 95% of U max, more preferably the rate is designed to limit the range of up to about 90% of U max (see page 7; meets claims 11-13). In order to obtain the benefits of prolonged fermentation and improved production yields, in the practice of the present method of limiting the feed rate of the carbon source, the rate of addition of the carbon source may be excessively limited so that the growth and / or It is recognized that production capacity is disadvantageously undesirably impaired. To that end, it is desirable to maintain the carbon source feed rate at a desired level, but to maintain a carbon source feed rate sufficient to avoid adversely affecting extracellular material growth and / or production (see page 8; meets claim 3).
In a preferred embodiment of the invention, the fermented broth is diluted with fresh fermentation medium and the carbon source feed rate is limited to a rate limiting level. Desirably, the method involves three phases: (1) inoculation phase; (2) batch feed growth phase; and (3) A continuous culture growth phase that limits the carbon source. The inoculation phase involves the supply of an inoculum of actively growing microorganisms to the fermentation vessel for 35 hours (meets claims 1 and 5). The pH of the medium was maintained at about pH 6.0. The dissolved oxygen content of the fermentation medium was maintained at 20% or more. An inoculum of actively growing microorganisms was introduced into the fermentation medium. During the course of the fermentation, the results were evaluated over a temperature range of 30C to 40C. (see example 1, page 11; meets claim 1).
The batch fed growth phase involves the growth of microorganisms in a fermentation vessel with continuous addition of medium, while maintaining the carbon source concentration at 5 g /or less. Typically, the carbon source concentration is between about 1 g / and about 5 g /or less during the batch feed phase. While changing from the batch feed phase to the steady state continuous phase, the continuous feed rate of fresh fermentation medium containing the carbon source is gradually increased. The continuous fermentation phase begins when the desired steady-state cell concentration has been achieved (see page 8; meeting limitations of claim 1 and 3).
With respect to temperature, it has been found that maximum growth of heterotrophic algae can be achieved over a specific temperature range of between about 30 ° C and about 38 ° C and between 33 ° C and about 38 ° It has also been found that controlling pH in fermentation of heterotrophic algae is important for maximizing growth. In particular, heterotrophic algae are about pH 5.5 and about pH 5.5. It was found to have a maximum growth rate between 6.5. Similar circumstances exist for other parameters, such as temperature, dissolved oxygen concentration and carbon dioxide concentration, and are described in detail in connection with the following examples. Dissolved oxygen concentrations equal to or greater than 10% (see page 9, meets claim 18).
As it pertains to claim 19, the method steps of the prior art is identical to those that have been claimed, the Office takes the position that the culture solution discharged from the vessel comprises microorganisms at 1 x 109 cells/mL or greater, absent evidence to the contrary. Conclusion
8. No claim is allowed.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKIA J JACKSON-TONGUE whose telephone number is (571)272-2921. The examiner can normally be reached Monday-Friday 930AM-530PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary B Nickol can be reached at 571-272-0835. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAKIA J JACKSON-TONGUE/Examiner, Art Unit 1645 October 18, 2025
/BRIAN GANGLE/Primary Examiner, Art Unit 1645