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 2-3, 5-7 are canceled. Claims 1, 4 and 8-12 are pending and under consideration in this action.
Priority
The instant claims are entitled to an effective filing date of 12/08/2020.
Response to Amendment
The amendment filed 06/17/2025 is entered.
The § 112(b) rejection of claim 4 is withdrawn in light of the amendment. However, a new § 112(b) rejection necessitated by amendment is addressed below.
Applicant's amendments and arguments filed on 06/17/2025 have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Objections
(New objection) Claim 4 is objected to because of the following informalities:
Claim 4 recites “The fermentation process of claim 1 the genus of”, which is ungrammatical and should be replaced with “The fermentation process of claim 1, wherein the genus of”.
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.
(New rejection necessitated by amendment) Claim 4 is 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 4 recites “the genus of Clostridium is selected from the group consisting of Clostridium ljungdahlii, Clostridium autoethanogum, Clostridium carboxidivorans, Clostridium drakei, Clostridium coskatiii, Clostridium ragsdalei, and a mixture thereof”, which is indefinite because it is unclear how a group or genus of Clostridium can be selected from a Markush group of Clostridium species. In other words, “the genus of Clostridium” describes a taxonomic category that ranks above species. Whereas, Clostridium ljungdahlii, Clostridium autoethanogum, Clostridium carboxidivorans, Clostridium drakei, Clostridium coskatiii, and Clostridium ragsdalei are species within the Clostridium taxonomic category. Therefore, it is unclear how a genus can be selected from a species. Moreover, it is unclear whether claim 4 intends to limit one, some, or all of the acetogenic bacteria required in claim 1. To obviate this rejection, claim 4 may be amended to recite “The fermentation process of claim 1, wherein the one or more acetogenic bacteria are selected from the group consisting of Clostridium ljungdahlii, Clostridium autoethanogum, Clostridium carboxidivorans, Clostridium drakei, Clostridium coskatiii, Clostridium ragsdalei, and a mixture thereof”.
Response to Arguments
Applicant's arguments filed 06/17/2025 regarding the §112(b) rejection of claim 4 have been fully considered but they do not apply to the new grounds of rejection set forth above. See the second paragraph on page 4 of the remarks.
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.
(Maintained) Claims 1, 4, and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Gaddy (2007) U.S. Patent No. 7,285,402 B2 (as provided in the IDS filed 12/02/2021), in view of Phillips Applied biochemistry and biotechnology, 1993, 39, 559-571 (as previously relied upon) and Phillips (hereafter Phillips (1994)) Applied biochemistry and biotechnology, 1994 45, 145-157.
Regarding claims 1, Gaddy teaches a continuous method for producing ethanol from the anaerobic bacterial fermentation of a caseous substrate comprising carbon monoxide, the method comprises: culturing in a fermentation bioreactor anaerobic, acetogenic C. ljungdahlii bacteria in a continuously fed liquid nutrient medium to provide a fermentation broth and supplying to said fermentation bioreactor said gaseous substrate comprising carbon monoxide, such as carbon monoxide and hydrogen. See claims 1 and 6 of Gaddy. In example 6, Gaddy teaches fermenting C. ljungdahlii in a continuous stirred tank reactor (CSTR) (e.g. fermenter) with a feed gas containing 57% H2 and 36% CO. See column 22 lines 62-66. Thus, Gaddy indicates that the feed gas contains a molar ratio of 22.26 H2/ CO because 57% H2 is equivalent to 57 g H2 for every 100 g syngas, and 36% CO is equivalent to 36 g of CO for every 100 g syngas; there are approximately 2 g/mol in H2 and 28 g/mol in CO, so every 100g syngas includes 28.5 moles of H2 and 1.28 moles of CO and 28.5moles H2/1.28moles CO= 22.2 moles H2/moles CO. In example 6, Gaddy teaches feeding a liquid medium containing excess salts, vitamins (including pantothenate) and trace metals to the reactor. See column 23 lines 1-2. The vitamin solution contains 50.6 mg/L thiamine HCl (vitamin B1), 50.5 mg/L pantothenic acid (vitamin B5), and 20.6 mg/L d-biotin (vitamin B7). See table 1. In analyzing parameters for ethanol production, Gaddy discloses that the ratio of the pantothenate (vitamin B5) fed to the cell production is 97 µg pantothenate/g-cell produced. Gaddy suggests that this level is sufficiently high to assure that pantothenate is not limiting. See column 23 lines 13-16 and table 2. Under these conditions, the cell concentration is 2.7g/L and ethanol productivity is 29 g/L·day. See column 23 lines 7-12 and table 2. Thus, Gaddy implies that the ethanol productivity rate is 10.7 g/day/gram cells because 29 g/L·day ÷2.7g cells/L is 10.7 g/day/gram cells. Gaddy teaches cell retention times between 6 and 25 hours. See column 34 lines 66-67.
In summation, Gaddy teaches a fermentation process comprising: providing a CO-containing gaseous substrate to a fermentor that includes a fermentation broth, wherein the CO-containing gaseous substrate has a H2 / CO molar ratio of 22.2, which meets the instantly claimed range of 0.2 or more. Gaddy teaches feeding a vitamin solution with vitamins B1, B5, and B7 to the fermentation broth, wherein a feed rate of vitamin B5 is 97 µg/g-cell produced, which is within the instantly claimed range of 25 to 150 µg/g cell produced. Gaddy teaches fermenting the CO-containing gaseous substrate with Clostridium ljungdahlii, an acetogenic bacteria. Gaddy teaches retention times between 6 and 25 hours, which overlaps with the instantly claimed 15 hour or less limitation. Last, Gaddy teaches a process that provides a specific ethanol productivity rate of 10.7 g/day/gram cells, which meets the instantly claimed more than 10 g/day/gram cells range.
Gaddy does not teach providing vitamin B5 at a feed rate that is at least 4 times a feed rate of vitamin B7 (biotin), and at least 3.5 times a feed rate of vitamin B1 (thiamine).
Phillips indicates that reducing the concentration of B-vitamins in a Clostridium ljungdahlii fermentation medium can increase the ethanol-to acetate product ratio. See the second paragraph on page 563. Furthermore, Philips discloses that the relative amounts of ethanol and acetate can be controlled by nutritional factors. See the second paragraph on page 570.
Phillips (1994) teaches growing Clostridium ljungdahlii on H2 or CO for the production of ethanol. See the abstract and figure 6. Phillips (1994) teaches a CSTR (i.e. continuous stirred tank reactor) medium that includes 0.155 mg/L Ca-D-pantothenate, 0.040 mg/L biotin and 0.01 mg/L thiamine-HCl. See table 3. Therefore, Phillips (1994) implies that the CSTR medium includes vitamin B5 in an amount that is 3.875 times the amount of vitamin B7 and 15.5 times the amount of vitamin B1. Moreover, Phillips (1994) teaches a basal defined medium comprising 0.083 mg/L Ca-D-pantothenate, 0.033 mg/L biotin, and 0.083 mg/L thiamine-HCl. See table 3. Thus, Phillips (1994) implies that basal defined medium includes a vitamin B5 in an amount that is 2.515 times the amount of vitamin B7 and in an amount that is equivalent to the amount of vitamin B1.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to adjust the vitamin B7 and vitamin B1 feed rates of Gaddy in view of Phillips and the CSTR medium Phillips (1994). Doing so is mere optimization through routine experimentation. One would be motivated to optimize the vitamin feed rate of Gaddy because Phillips suggests that reducing the concentration of B-vitamins can increase the ethanol to acetate ratio. There would be a reasonable expectation of success because Gaddy demonstrates feeding, to a CSTR reactor, a vitamin solution containing vitamin B5 in an amount that is 2.45 times that of vitamin B7 and 0.998 times that of vitamin B1 (e.g. nearly equivalent); Phillips (1994) teaches a basal defined medium with similar B-vitamin proportions compared to Gaddy because the basal defined medium of Phillips (1994) contains vitamin B5 in an amount that is 2.515 times that of vitamin B7 and equivalent to that of vitamin B1; yet, Phillips (1994) also teaches a CSTR medium where vitamin B5 is an amount that is 3.875 times that of vitamin B7 and 15.5 times that of vitamin B1. Thus, one could have reasonably adjusted the vitamin B7 and vitamin B1 feed rates of Gaddy based on the B-vitamin proportions in the CSTR medium taught by Phillips (1994). MPEP 2144.05(II) states that “[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).
Regarding claim 4, Gaddy teaches acetogenic bacteria including Clostridium ljungdahlii. See column 6 lines 31 and 38-39 and column 22 line 63.
Regarding claim 8, Gaddy teaches an ethanol production medium that does not contain yeast extract. See table 1 in column 35. Gaddy also teaches using a rich medium containing 1 g/L yeast extract as an alternative to a nutrient medium containing vitamin B5 or calcium pantothenate. See column 17 line 66-66 and column 26 line 65.
Phillips suggests that the reduction of the B-vitamin concentration and elimination of yeast extract diminishes growth potential slightly but causes a significant increase in the ethanol-to-acetate product ratio. See the second paragraph on page 563.
It would have been obvious prior to the effective filing date of the instantly claimed invention to have used the ethanol production medium of Gaddy and in the process to have arrived at a fermentation broth that has 0.01 g/L or less yeast extract. One would be motivated to do so because Phillips suggests that eliminating yeast extract may contribute to an increase in the ethanol-to-acetate product ratio. There would have been a reasonable expectation of success because Gaddy suggested that yeast extract was not necessary, as the medium could be used as alternative.
Regarding claim 9, Gaddy teaches bacterial growth media without sugar. See column 6 line 61.
It would have been obvious prior to the effective filing date of the instantly claimed invention to have optimized the amount of carbohydrates in the sugarless fermentation media of Gaddy, and in the process to have arrived a fermentation broth with 0.01 g/L or less carbohydrates as instantly claimed. There would have been a reasonable expectation of success because Gaddy suggested that the sugarless (i.e. 0g/L) medium contained vitamins and minerals sufficient to permit growth. See column 6 lines 58-61.
Regarding claims 10, Gaddy teaches permeate, a cell free liquid, formed from the fermentation broth. See column 10 lines 3 to 7 for a description of permeate being separated. Gaddy teaches acetate production between 0-5 g/L from CO gas. Since 75% of acetic acid (CH3COOH) is carboxylic acid, Gaddy implies that the permeate has between 0-3.75 g/L of carboxylic acid from CO gas.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to have optimized the amount of carboxylic acid in the permeate by adjusting the flow of the CO-containing gaseous substrate and in the processes to have arrived at the instantly claimed 1 to 3 g/L carboxylic acid range as instantly claimed. There would have been a reasonable expectation of success because Gaddy suggested that acetate production is affected by CO gas. MPEP 2144.05(II) states that “[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).
Regarding claim 11, Gaddy teaches measuring acetate, which comprises carboxylic acid, within cell-free permeate samples through gas chromatography. See column 9, lines 29-33.
Instant claim 12 is interpreted as requiring any automatic analytical and control system, such as a New Brunswick Bioflow™ reactor, as disclosed in the instant specification in paragraph [0063].
Regarding claim 12, Gaddy teaches using New Brunswick Scientific Bioflo® reactor for adjusting gas rate levels. See column 18, line 3.
Response to Arguments
Applicant's arguments filed 06/17/2025 have been fully considered but they are unpersuasive.
§103 rejection of claims 1, 4, and 8-12 over Gaddy in view of Phillips and Phillips (1994):
Applicant argues that the inventive concept of the claimed process lies in economically increasing specific ethanol productivity with an unexpected and surprisingly optimized B vitamin combinations to improve industry competitiveness (see paragraph [0006] of the specification). Increasing specific ethanol productivity increases production and optimizing vitamin combinations reduces operation costs. See the third paragraph on page 4 of the remarks.
To the extent that this argument represents an attempt to overcome the prior art rejections by reliance on unexpected results, it is unpersuasive. Paragraph [0006] states that “there remains a strong need for processes and medium compositions with optimized B vitamins combination that economically increase specific ethanol productivity and thus improve industry competitiveness”. Therefore, paragraph [0006] does not provide any evidence for unexpected and surprisingly optimized B vitamin combinations, as argued. MPEP 716.02(b)-(e) indicates that unexpected results must be established by factual evidence. Since Applicant has not provided any factual evidence, the argument is unpersuasive.
Applicant argues that the claimed process describes a feed rate, not a concentration. See the last full paragraph on page 4. Applicant asserts that Gaddy does not teach: the feed rate of vitamin B1 as claimed; the feed rate of vitamin B7 as claimed; providing vitamin B5 at a feed rate that is at least 3.5 times the feed rate of B1; providing B5 at a feed rate that is at least 4 times the feed rate of B7; or high specific ethanol productivity with optimized vitamin combination. See the top of page 5 of the remarks.
This argument is unpersuasive because Gaddy directly teaches a vitamin B5 feed rate, in addition to teaching vitamin concentrations. Specifically, Gaddy teaches pantothenate (vitamin B5) fed to the cell production is 97 µg pantothenate/g-cell produced, which meets the instantly claimed vitamin B5 feed rate that is 25 to 150 µg/g cells produced. See column 23 lines 13-16 of Gaddy. Gaddy teaches feeding a liquid medium containing vitamins to a CSTR, and Gaddy teaches a vitamin solution that includes vitamins B5, B7 and B1 at different concentrations. Therefore, Gaddy indicates that vitamins B5, B7 and B1 are provided to the CSTR at the same time because they are all in the same vitamin solution. However, due to the concentration differences between the vitamins B5, B7 and B1 within the vitamin solution, the vitamins are provided at different µg/g-cell produced rates. Phillips and Phillips provide motivation to optimize the concentration of vitamins within that vitamin solution and, consequently, alter the vitamin feed rates.
Applicant argues that a previous statement made by Examiner is incorrect in view of Gaddy. Examiner stated, in the action mailed 03/24/2025, that “Gaddy teaches a “µg pantothenate/g-cell produced” unit and describes it as “the ratio of the pantothenate fed [past tense] to the cell production…The specification does not define the “cells produced” within the instantly claimed “µg/g cells produced” unit, so any cell mass present is considered to be produced”. Applicant asserts that the “µg/g cells produced” unit does not mean to consider any of the cell mass present. Gaddy, in lines 8-10 of column 20, explicitly says “[a]s shown in Table 2, the Ca-d-pantothenate fed per unit of cells produced was 1575 to 3150 micro-grams per unit gram of cells produced (ug/g-cell produced)”. As such, Applicant argues that the “µg pantothenate/g-cell produced” unit is not any cell mass present, but it is closely related to per unit of cells produced, which is the cell production rate within a unit of g/hour. Applicant argues that the vitamin feed rate is calculated by dividing vitamin flow rate (ug/hour) by cell production rate (g/hour). See page 5 of the remarks.
This argument is unpersuasive because MPEP 2111 states that pending claims must be "given their broadest reasonable interpretation consistent with the specification.” The specification does not teach a cell production rate in terms of g/hour, nor does the specification define the “cells produced” portion of the instantly claimed “µg/g cells produced” unit. Applicant indicates that the vitamin feed rate limitation should be interpreted in view of Gaddy. However, it is unclear how Applicant derived the vitamin feed rate calculation from the teachings of Gaddy. In column 20 lines 8-10, Gaddy states “per unit of cells produced….(ug/g-cells-produced)”, which indicates that the unit of cells produced is in grams. Applicant’s argument implies that the vitamin feed rate calculation requires a temporal element. However, the claims do not require providing vitamins B1, B5, and B7 to the fermentation broth for any specific period of time; and the specification does not teach using a cell production rate to determine a vitamin feed rate. There is no evidence of record that indicates that a “vitamin feed rate” is ordinarily calculated by dividing vitamin flow rate (µg/hour) by cell production rate (g/hour); nor is there evidence to suggest that such calculation is necessary to arrive that the “µg/g cells produced” limitation. As such, the argument is unpersuasive because the instant claims are interpreted in view of the specification, and there is no evidence of record indicating that the “µg/g cells produced” limitation should be interpreted otherwise due to its ordinary meaning in the art.
Applicant argues that Phillips, also referred to as Phillips (1993) by Applicant, does not teach the feed rates of vitamin B1, B5 or B7 as claimed; Phillips does not teach providing B5 at a feed rate that is at least 4 times the feed rate of B7 as claimed; and Phillips does not teach high specific ethanol productivity with optimized vitamin combinations. Applicant asserts that Phillips may provide enough data to calculate the vitamins’ feed rate. See pages 5-6 of the remarks. Phillips does not directly provide the cell production rate or the cell growth rate for the experiment. Instead, Phillips shows the cell concentration throughout the experiment. See the paragraph spanning pages 6-7 of the remarks. Applicant asserts that the vitamin feed rates of Phillips are much higher than the claimed range. See the first paragraph on page 8.
This argument is unpersuasive because one cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Phillips is not relied upon for teaching the vitamin feed rates. Rather, Gaddy is relied upon for directly teaching the instantly claimed “µg/g cells produced unit”, and Phillips is relied upon for providing motivation to optimize the vitamin concentrations in the vitamin solution of Gaddy for ethanol production.
Applicant argues that, although Phillips suggests that reducing the concentration of B-vitamins can increase the ethanol to acetate ratio, Phillips also mentions that biotin, thiamine-HCl and Ca-D-pantothenate are required B-vitamins, which means a minimum amount of those vitamins is required because the bacteria cannot produce them by itself. Applicant argues that examples 2-4 of the instant application show that vitamins B1 and B7 could be lowered to a low amount but B5 is required to maintained at a relatively higher amount to keep the ethanol productivity. Hence, Applicant argues that Gaddy and Philips (1993) do not describe or suggest the claimed ratios and resulting much lower amounts of vitamins could provide an ethanol productivity as claimed. See the last full paragraph on page 8 of the remarks.
This argument is unpersuasive because Phillips is not relied upon for teaching the instantly claimed ethanol productivity. Rather, Gaddy is relied upon for teaching that element. To the extent that Applicant is relying on examples 2-4 of the instant specification as support for unexpected results, it is unpersuasive. Example 2 is not commensurate in scope with the instant claims because the thiamine (B1) feed in example 2 is higher than that of the pantothenate (B5), such that the example does not meet the claimed limitation requiring the vitamin B5 to be “provided at a feed rate that is at least 3.5 times a feed rate of vitamin B1”. See paragraph [0061] of the instant specification. Example 3 includes 3 experiments that are commensurate in scope with the instant claims. See the last 3 rows of the table in paragraph [0063]. However, the way in which the results of example 3 are unexpected over the prior art of Gaddy, Phillips and Phillips (1994) is unclear. In other words, there is no evidence of record indicating that the vitamins B1 and B7 levels disclosed in example 3 are surprisingly lower than the prior art. As discussed above, Phillips provides motivation to reduce the concentration of B-vitamins in a Clostridium ljungdahlii fermentation medium. Furthermore, example 4 is not commensurate in scope with the instant claims because the specific ethanol productivity rates are below 8 g/day/gam cells. See paragraph [0065] of the instant specification. Thus, the argument that the disclosed results are unexpected over Phillips is unpersuasive.
Applicant argues that Phillips (1994) does not cure the deficits of Gaddy and Phillips because Phillips (1994) teaches batch processes. The only continuous process was the seed culture for the batch experiments. Applicant argues that the CSTR medium composition of Phillips (1994) is for the seed inoculation continuous process. Applicant asserts that Phillips (1994) fails to provide anything on medium flow rate, cell concentration, purge rate, and cell production rate. It is impossible to calculate how much vitamin B1, B5 and B7 is used during the continuous process of Phillips (1994). As such, Phillips (1994) does not provide any meaningful information on vitamin consumption and optimization. See the first paragraph on page 9.
This argument is unpersuasive because Phillips (1994) is not relied upon for teaching the instantly claimed vitamin feed rate; and the instant claims do not require a medium flow rate, cell concentration, purge rate or cell production rate. Applicant indicates that Phillips (1994) teaches away from the instant invention because Phillips (1994) teaches a batch culture and only a seed inoculation continuous process. However, the instant claims do not explicitly require the fermentation process to be a continuous process. Moreover, the test for obvious is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the instant case, the teachings of Phillips and Phillips (1994) suggest optimizing the vitamin ratios in the vitamin solution of Gaddy.
Applicant argues that the underlying invention not only finds a ratio between vitamin B5 and vitamins B1 and B7, but also gives out the minimum amounts of vitamins B1 and B7 needed per gram of cells produced in the bioreactor. It further optimized the vitamin B5 usage to maximum ethanol production. None of Gaddy, Phillips and Phillips (1994) provide the minimum amounts of vitamins B1 and B7 needed or suggest anything about vitamin optimization. See the last paragraph on page 9.
This argument is unpersuasive because Phillips suggests optimizing the B-vitamin concentrations in a Clostridium ljungdahlii fermentation medium, as it can increase the ethanol-to acetate product ratio. See the second paragraph on page 563. Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). In the instant case, Phillips provides motivation for optimizing the B-vitamins in the vitamin solution of Gaddy, and Phillips (1994) is relied upon for teaching the ratio of B-vitamins. Applicant argues that the instant invention finds a ratio between vitamin B5 and vitamins B1 and B7 that is needed for maximum ethanol production. However, this argument is not commensurate in scope with the instant claims because the instantly claimed ethanol “productivity rate of 10 g/day/gram cells or more” does not include an upper limit or maximum for the ethanol production.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
(Maintain) Claims 1, 4 and 8-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-11 of U.S. Patent No. 10,100,336 B2 to Scott et al. (hereinafter Scott ‘336) in view of Gaddy (US 7,285,402 B2), Phillips (Applied biochemistry and biotechnology, 39, 1993, 559-571) and Phillips (1994) (Applied biochemistry and biotechnology, 1994 45, 145-157).
Claims 1 of Scott ‘336 recites a fermentation process comprising fermenting syngas in a fermentation medium with acetogenic bacteria, the process effective for providing a specific STY of at least about 1 gram of ethanol/(L∙day∙gram cells),
wherein the fermentation medium includes
at least 112 to 125 mg of nitrogen per gram of cells,
at least 10.5 to 15 mg of phosphorous per gram of cells, and
at least 26 to 36 mg of potassium per gram of cells,
wherein the fermentation medium has less than 0.025 ppm boron, less than 0.0025 ppm manganese, less than 0.001 ppm molybdenum, and less than 0.01 ppm copper and wherein the fermentation medium has less than 0.01 g/L carbohydrates and less than 0.01 g/L yeast extract.
Claim 7 of Scott ‘336 recites the fermentation process of claim 1 wherein the syngas has a CO/CO2 ratio of at least about 0.75.
Claim 8 of Scott ‘336 recites the fermentation process of claim 1 wherein the acetogenic bacteria is selected from the group consisting of… Clostridium aceticum, Clostridium acetobutylicum, Clostridium autoethanogenum DSM 19630 of DSMZ Germany, Clostridium autoethanogenum DSM 10061 of DSMZ Germany, Clostridium autoethanogenum DSM 23693 of DSMZ Germany, Clostridium autoethanogenum DSM 24138 of DSMZ Germany, Clostridium carboxidivorans P7 ATCC PTA-7827, Clostridium coskatii ATCC PTA-10522, Clostridium drakei, Clostridium ljungdahlii PETC ATCC 49587, Clostridium ljungdahlii ERI2 ATCC 55380, Clostridium ljungdahlii C-01 ATCC 55988, Clostridium ljungdahlii O-52 ATCC 55889, Clostridium magnum, Clostridium pasteurianum DSM 525 of DSMZ Germany, Clostridium ragsdali P11 ATCC BAA-622, Clostridium scatologenes, Clostridium thermoaceticum, Clostridium ultunense, and mixtures thereof.
The patent claims of Scott ‘336 lack providing a gaseous substrate to a fermentor that includes a fermentation broth, wherein the CO-containing gaseous substrate has a H2/CO molar ratio of 0.2 or more; providing vitamin B1, B5, and B7 to a fermentation broth, wherein a feed rate of vitamin B5 is 25 to 150 ug/g cell produced, wherein an amount of vitamin B is provided at a feed rate of at least 4 times as feed rate of vitamin B7, and the amount of vitamin B5 is provided at a feed rate that is at least 3.5 times a feed rate of vitamin B1; and a cell retention time of 15 hours or less, wherein the process provides a specific ethanol productivity rate of 10 g/day/gram cells or more (relevant to instant claim 1). The patent claims of Scott ‘336 lack a permeate formed from the broth and the process maintains a carboxylic acid concentration of 1 to 3 g/L in the permeate through adjusting a gas flow rate of the CO-containing gaseous substrate (relevant to instant claim 10). The patent claims of Scott ‘336 lack a carboxylic acid concentration measured by an analytical technique selected from the group consisting of near infrared spectroscopy (NIR), gas chromatography, high pressure liquid chromatography, mass spectroscopy and combination thereof (relevant to instant claim 11). The patent claims of Scott ‘336 lack a gas flow rate of the CO-containing gaseous substrate is adjusted by an automated analytical and control system (relevant to instant claim 12).
However, Gaddy teaches fermenting C. ljungdahlii with a feed gas containing 57% H2 and 36% CO, which is a H2 / CO molar ratio of 22.2. See column 22 lines 62-66. Gaddy teaches feeding vitamin B5 at 97 µg/g-cell produced. See column 23 lines 13-16 and table 2. Gaddy teaches retention times between 6 and 25 hours. See column 34 lines 66-67. Gaddy a cell concentration is 2.7g/L and an ethanol productivity is 29 g/L·day, which is 10.7 g/day/gram cells. See column 23 lines 7-12 and table 2. Phillips indicates that reducing the concentration of B-vitamins in a Clostridium ljungdahlii fermentation medium can increase the ethanol-to acetate product ratio. See the second paragraph on page 563. Phillips (1994) teaches a medium that includes 0.155 mg/L Ca-D-pantothenate, 0.040 mg/L biotin and 0.01 mg/L thiamine-HCl. See table 3 (relevant to instant claim 1). Gaddy implies that the permeate has between 0-3.75 g/L of carboxylic acid from CO gas. See column 10 (relevant to instant claim 10). Gaddy teaches measuring acetate, which comprises carboxylic acid, within cell-free permeate samples through gas chromatography. See column 9, lines 29-33 (relevant to instant claim 11). Gaddy teaches using a New Brunswick automated analytical control system. See column 18 line 3 (relevant to instant claim 12).
It would have been obvious to a person of ordinary skill in the art, prior to the effective filing date, to modify the fermentation process of Scott ‘336 by adding vitamins B1, B5 and B7 of Gaddy to the fermentation medium of Scott ‘336; by optimizing the B-vitamin feed rates of Gaddy in view of Phillips and Phillips (1994); by optimizing the cell retention time in view of Gaddy; and by further optimizing the H2 to CO molar ratio in the syngas of Scott ‘336 in view of Gaddy in order to ferment Clostridium for ethanol production.
(Maintain) Claims 1, 4 and 8-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5 of U.S. Patent No. 9,193,947 B2 to Senaratne et al. (hereinafter Senaratne ‘947) in view of Gaddy (US 7,285,402 B2), Phillips (Applied biochemistry and biotechnology, 39, 1993, 559-571) and Phillips (1994) (Applied biochemistry and biotechnology, 1994 45, 145-157).
Claim 1 of Senaratne ‘947 recites a process for culturing acetogenic bacteria on syngas, the process comprising: culturing the acetogenic bacteria on a first substrate to provide a cell density of at least about 0.005 g/L, wherein the first substrate includes a carbon source selected from the group consisting of yeast extract, carbohydrates, alcohol, amino acids, peptone, peptides, protein, fatty acids, lipid and mixtures thereof; sporulating the acetogenic bacteria by replacing at least a portion of the first substrate with syngas having at least about 10 mole % CO and replacing at least a portion of a first medium with a production medium to convert at least a portion of the bacteria to spores, wherein the sporulating provides a spore number to cell number ratio of about 0.05 or more; and germinating the spores in the production medium at a pH of about 4.1 to about 5 with syngas having at least about 10 mole % CO to provide a specific CO uptake of at least about 0.25 mmole/min/gram of cells and a space time yield (STY) of about 1 g or more ethanol/(L·day gram cells).
Claim 2 of Senaratne ‘947 recites the process of claim 1 wherein the syngas has a CO/CO2 molar ratio of at least about 0.75.
Claim 3 of Senaratne ‘947 recites the process of claim 1 wherein the acetogenic bacterium is selected from the group consisting of… Clostridium aceticum, Clostridium acetobutylicum, Clostridium acetobutylicum P262 (DSM 19630 of DSMZ Germany), Clostridium autoethanogenum (DSM 19630 of DSMZ Germany), Clostridium autoethanogenum (DSM 10061 of DSMZ Germany), Clostridium autoethanogenum (DSM 23693 of DSMZ Germany), Clostridium autoethanogenum (DSM 24138 of DSMZ Germany), Clostridium carboxidivorans P7 (ATCC PTA-7827), Clostridium coskatii (ATCC PTA-10522), Clostridium drakei, Clostridium ljungdahlii PETC (ATCC 49587), Clostridium ljungdahlii ERI2 (ATCC 55380), Clostridium ljungdahlii C-01 (ATCC 55988), Clostridium ljungdahlii O-52 (ATCC 55889), Clostridium magnum, Clostridium pasteurianum (DSM 525 of DSMZ Germany), Clostridium ragsdali P11 (ATCC BAA-622), Clostridium scatologenes, Clostridium thermoaceticum, Clostridium ultunense.
The patent claims of Senaratne ‘947 lack providing a gaseous substrate to a fermentor that includes a fermentation broth, wherein the CO-containing gaseous substrate has a H2/CO molar ratio of 0.2 or more; providing vitamin B1, B5, and B7 to a fermentation broth, wherein a feed rate of vitamin B5 is 25 to 150 µg/g cell produced, wherein an amount of vitamin B is provided at a feed rate of at least 4 times a feed rate of vitamin B7, and the amount of vitamin B5 is provided at a feed rate that is at least 3.5 times a feed rate of vitamin B1; and a cell retention time of 15 hours or less, wherein the process provides a specific ethanol productivity rate of 10 g/day/gram cells or more (relevant to instant claim 1). The patent claims of Senaratne ‘947 lack a permeate that is formed from the broth and a process that maintains a carboxylic acid concentration of 1 to 3 g/L in the permeate through adjusting a gas flow rate of the CO-containing gaseous substrate (relevant to instant claim 10). The patent claims of Senaratne ‘947 lack a carboxylic acid concentration measured by an analytical technique selected from the group consisting of near infrared spectroscopy, gas chromatography, high pressure liquid chromatography, mass spectroscopy and combinations thereof (relevant to instant claim 11). The patent claims of Senaratne ‘947 lack a gas flow rate of the CO-containing gaseous substrate that is adjusted by an automated analytical and control system (relevant to instant claim 12).
However, Gaddy teaches fermenting C. ljungdahlii with a feed gas containing 57% H2 and 36% CO, which is a H2 / CO molar ratio of 22.2. See column 22 lines 62-66. Gaddy teaches feeding vitamin B5 at 97 µg/g-cell produced. See column 23 lines 13-16 and table 2. Gaddy teaches retention times between 6 and 25 hours. See column 34 lines 66-67. Gaddy a cell concentration is 2.7g/L and an ethanol productivity is 29 g/L·day, which is 10.7 g/day/gram cells. See column 23 lines 7-12 and table 2. Phillips indicates that reducing the concentration of B-vitamins in a Clostridium ljungdahlii fermentation medium can increase the ethanol-to acetate product ratio. See the second paragraph on page 563. Phillips (1994) teaches a CSTR medium that includes 0.155 mg/L Ca-D-pantothenate, 0.040 mg/L biotin and 0.01 mg/L thiamine-HCl. See table 3. Therefore, Phillips (1994) implies that the CSTR medium includes vitamin B5 in an amount that is 3.875 times the amount of vitamin B7 and 15.5 times the amount of vitamin B1 (relevant to instant claim 1). Gaddy implies that the permeate has between 0-3.75 g/L of carboxylic acid from CO gas. See column 10 (relevant to instant claim 10). Gaddy teaches measuring acetate, which comprises carboxylic acid, within cell-free permeate samples through gas chromatography. See column 9, lines 29-33 (relevant to instant claim 11). Gaddy teaches using a New Brunswick automated analytical control system. See column 18 line 3 (relevant to instant claim 12).
It would have been obvious to a person of ordinary skill in the art, prior to the effective filing date, to modify the process for culturing acetogenic bacteria of Senaratne ‘947 by adding the vitamins B1, B5 and B7 of Gaddy to the first substrate of Senaratne ‘947; by optimizing the B-vitamin feed rates of Gaddy in view of Phillips and Phillips (1994); and by finally modifying the molar ratio of H2 and CO in the syngas in view of Gaddy in order to ferment a Clostridium acetogenic bacteria for ethanol production. Since Senaratne ‘947 claims a first substrate that includes a carbon source selected from the group consisting of yeast extract, carbohydrates, alcohol, amino acids, peptone, peptides, protein, fatty acids, lipid and mixtures thereof, it would have been obvious to select an alcohol, amino acids, peptone, peptides, protein, fatty acids, or lipid from the list and in the process to arrive at a broth with 0g/L yeast extract and 0g/L carbohydrates (relevant to instant claims 8-9).
(Maintain) Claims 1, 4 and 8-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10,131,872 B2 to Senaratne et al. (hereinafter Senaratne ‘872) in view of Gaddy (US 7,285,402 B2), Phillips (Applied biochemistry and biotechnology, 39, 1993, 559-571) and Phillips (1994) (Applied biochemistry and biotechnology, 1994 45, 145-157).
Claim 1 of Senaratne ‘872 recites a process for fermenting a carbon monoxide (CO)-containing gaseous substrate comprising: growing an inoculum of acetogenic bacteria cells on a first medium that includes a first substrate to provide a cell density of about 0.02 g/L or more, wherein the first medium has a pH of 5.5 to 7.0 and the first substrate includes a carbon source that is selected from the group consisting of yeast extract, carbohydrates, alcohol, amino acids, peptone, peptides, protein, fatty acids, lipid and mixtures thereof, wherein the inoculum of acetogenic bacteria has no measurable consumption of a (CO)-containing gaseous substrate; sporulating at least a portion of the inoculum of bacteria by reducing an amount of the first substrate to provide bacterial spores; germinating the bacterial spores by replacing at least a portion of the first medium with a production medium having a pH of 4.1 to 5 and by replacing at least a portion of the first substrate with a CO-containing gaseous substrate, wherein the CO is a sole carbon source in the production medium; and supplying the CO-containing gaseous substrate to maintain a specific CO uptake of about 0.25 mmol per g cells or more; wherein the process of fermenting CO provides a specific STY (space time yield) of about 1 g of ethanol/(L day gram cells) or more.
Claim 2 of Senaratne ‘872 recites the process of claim 1 wherein the CO containing gaseous substrate is syngas.
Claim 3 of Senaratne ‘872 recites the process of claim 2 wherein the syngas has a CO/CO2 molar ratio of at least about 0.75.
Claim 4 of Senaratne ‘872 recites the process of claim 1 wherein the acetogenic bacteria is selected from the group consisting of…Clostridium aceticurn, Clostridium acetobutylicum, Clostridium acetobutylicum P262 (DSM 19630 of DSMZ Germany), Clostridium autoethanogenum (DSM 19630 of DSMZ Germany), Clostridium autoethanogenum (DSM 10061 of DSMZ Germany), Clostridium autoethanogenum (DSM 23693 of DSMZ Germany), Clostridium autoethanogenum (DSM 24138 of DSMZ Germany), Clostridium carboxidivorans P7 (ATCC PTA-7827), Clostridium coskatii (ATCC PTA-10522), Clostridium drakei, Clostridium ljungdahlii PETC (ATCC 49587), Clostridium ljungdahlii ERI2 (ATCC 55380), Clostridium ljungdahlii C-01 (ATCC 55988), Clostridium ljungdahlii O-52 (ATCC 55889), Clostridium magnum, Clostridium pasteurianum (DSM 525 of DSMZ Germany), Clostridium ragsdali P11 (ATCC BAA-622), Clostridium scatologenes, Clostridium thermoaceticum, Clostridium ultunense.
The patent claims of Senaratne ‘872 lack providing a gaseous substrate to a fermentor that includes a fermentation broth, wherein the CO-containing gaseous substrate has a H2/CO molar ratio of 0.2 or more; providing vitamin B1, B5, and B7 to a fermentation broth, wherein the feed rate of vitamin B5 is 25 to 150 µg/g cell produced, wherein an amount of vitamin B is provided at a feed rate of at least 4 times as feed rate of vitamin B7, and the amount of vitamin B5 is provided at a feed rate that is at least 3.5 times a feed rate of vitamin B1; and a cell retention time of 15 hours or less, wherein the process provides a specific ethanol productivity rate of 10 g/day/gram cells or more (relevant to instant claim 1). The patent claims of Senaratne ‘872 lack a fermentation broth that has 0.01 g/L or less yeast extract (relevant to instant claim 8), or has 0.01g/L or less carbohydrates (relevant to instant claim 9). The patent claims of Senaratne ‘872 lack a permeate formed from the broth and the process maintains a carboxylic acid concentration of 1 to 3 g/L in the permeate through adjusting a gas flow rate of the CO-containing gaseous substrate(relevant to instant claim 10). The patent claims of Senaratne ‘872 lack a carboxylic acid concentration measured by an analytical technique selected from the group consisting of near infrared spectroscopy (NIR), gas chromatography, high pressure liquid chromatography, mass spectroscopy and combination thereof (relevant to instant claim 11). The patent claims of Senaratne ‘872 lack a gas flow rate of the CO-containing gaseous substrate is adjusted by an automated analytical and control system (relevant to instant claim 12).
However, Gaddy teaches fermenting C. ljungdahlii with a feed gas containing 57% H2 and 36% CO, which is a H2 / CO molar ratio of 22.2. See column 22 lines 62-66. Gaddy teaches feeding vitamin B5 at 97 µg/g-cell produced. See column 23 lines 13-16 and table 2. Gaddy teaches retention times between 6 and 25 hours. See column 34 lines 66-67. Gaddy a cell concentration is 2.7g/L and an ethanol productivity is 29 g/L·day, which is 10.7 g/day/gram cells. See column 23 lines 7-12 and table 2. Phillips indicates that reducing the concentration of B-vitamins in a Clostridium ljungdahlii fermentation medium can increase the ethanol-to acetate product ratio. See the second paragraph on page 563. Phillips (1994) teaches a CSTR medium that includes 0.155 mg/L Ca-D-pantothenate, 0.040 mg/L biotin and 0.01 mg/L thiamine-HCl. See table 3. Therefore, Phillips (1994) implies that the CSTR medium includes vitamin B5 in an amount that is 3.875 times the amount of vitamin B7 and 15.5 times the amount of vitamin B1 (relevant to instant claim 1). Gaddy teaches an ethanol production medium that does not contain yeast extract (relevant to instant claim 8). See table 1 in column 35. Gaddy teaches bacterial growth media without sugar (relevant to instant claim 9). Gaddy implies that the permeate has between 0-3.75 g/L of carboxylic acid from CO gas. See column 10 (relevant to instant claim 10). Gaddy teaches measuring acetate, which comprises carboxylic acid, within cell-free permeate samples through gas chromatography. See column 9, lines 29-33 (relevant to instant claim 11). Gaddy teaches using a New Brunswick automated analytical control system. See column 18 line 3 (relevant to instant claim 12).
It would have been obvious to a person of ordinary skill in the art, prior to the effective filing date, to modify the fermentation process of Senaratne ‘872 by adding vitamins B1, B5 and B7 in view of Gaddy; by optimizing the B-vitamin feed rates of Gaddy in view of Phillips and Phillips (1994); by modifying the molar ratio of H2 and CO in the syngas in view Gaddy; and by further optimizing the cell retention and the amount of the yeast extract and the carbohydrates in the first substrate of Senaratne ‘872 in view of Gaddy and Phillips in order to ferment acetogenic bacteria for ethanol production.
(Maintain) Claims 1, 4 and 8-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,337,074 B2 to Senaratne et al. (hereinafter Senaratne‘337) in view of Gaddy (US 7,285,402 B2), Phillips (Applied biochemistry and biotechnology, 39, 1993, 559-571) and Phillips (1994) (Applied biochemistry and biotechnology, 1994 45, 145-157).
Claim 9 of Senaratne ‘074 recites a method of producing, one or more alcohols from a gaseous substrate, the method comprising: adding gaseous substrate comprising carbon monoxide (CO) and hydrogen (H2) into an aqueous medium in a bioreactor, wherein the aqueous medium includes one or more anaerobic acetogenic microorganisms; agitating the aqueous medium at an agitator speed of 10 to 1000 rpm; measuring conversion of CO; measuring conversion of H2; and increasing a flow rate of gaseous substrate into the bioreactor by a flow factor (proposed quantity of gaseous feed divided by current quantity of gaseous feed) of 1.05 to 2.0 when CO conversion in the bioreactor is 25 to 95%, H2 conversion in, the bioreactor is 25 to 95% and a difference between CO conversion and H2 conversion in the bioreactor is 0% to 25%, wherein the agitator speed is increased when a second CO conversion is 0 to 25% and H2 conversion is 0 to 25%; wherein if a concentration of acetic acid in the aqueous medium is less than about 1.5 grams per liter after reaching a cell density of at least 50% more than an initial cell density, then about 1 ml of