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 .
Election/Restrictions
Applicant’s election without traverse of Invention I (claims 1-17) in the reply filed on 12/18/2025 is acknowledged.
Claims 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-17 are directed to the elected invention and have been examined on their merits.
Priority
The present application claims benefit of U.S. provisional application 63/387,060 (filed on 12/12/2022).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/14/2024 is in compliance with the provisions of 37 C.F.R. 1.97. All references cited in this IDS have been fully considered.
Claim Objections
Claim 4 is objected to because line 10 contains a misspelling of the word “dehydrogenase”.
Claim 4 is further objected to because the second closing parenthesis (“)”) should be removed from line 10.
Claim 4 is further objected to because “coA” should be changed to “CoA” in line 6 in order to maintain consistency with the use of the same word in line 3 (and elsewhere in the claims).
Claim 7 is objected to because the word “of” should be removed in line 1.
Claim 7 is further objected to because line 1 contains a misspelling of the word “heterologous”.
Claim 11 is objected to because a period should be added at the end of the claim.
Claim 14 is objected to because the word “wherein” should be added after “claim 1” in line 1.
Claim 16 is objected to because the word “converting” in line 6 should be replaced with “the conversion of” to maintain consistent language with the antecedent phrases in claim 1. Alternatively, claim 1 should be amended to replace “the conversion of” in lines 6-7 with “converting”.
Claim 16 is further objected to because a hyphen should be added between “dihydroxyacetone” and “phosphate” to maintain consistent language with line 7 of claim 1. Alternatively, the hyphen should be removed from the term in line 7 of claim 1.
Claim 17 is objected to because the word “of” should be added after “combination” in claim 1.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112:
(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.
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 7 and 10 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.
Claim 7 depends from claim 1 which requires a third metabolic pathway comprising one or more third heterologous polypeptides. Claim 7 limits the type of polypeptide and this limitation includes “a native or heterologous polypeptide”. It is unclear how the heterologous polypeptide of this claim can be a “native” polypeptide because the term “heterologous” excludes native polypeptides.
In the interest of compact prosecution, this claim has been examined for native or heterologous polypeptides, as written.
Claim 10 is indefinite because it recites a relative term (“decreased”) with no apparent comparison. Specifically, the claim recites “the bacterial host cell has a decreased lactate dehydrogenase activity”. It is not clear what the decreased lactate dehydrogenase activity is compared to. Accordingly, the claim is indefinite.
In the interest of compact prosecution, this claim has been examined as if it requires that the bacterial host cell has a decreased lactate dehydrogenase activity “when compared to a control bacterial host cell” (similar to claim language in claim 11).
Claim 7 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 7 broadens rather than narrows the scope of claim 1 because it allows for the one or more third polypeptide to be “native”. Claim 1 requires that the polypeptide is “one or more third heterologous polypeptides”. Accordingly, this phrase necessarily excludes native polypeptides.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 101
Subject matter eligibility has been fully considered for each of the elected composition claims. Although bacteria and yeast exist in nature (i.e., are products of nature or natural phenomena), each of the claims requires a bacterial host which has a third heterologous polypeptide for converting pyruvate into ethanol. Because the polypeptide is required to be heterologous, the bacterial host cell required by each of the claims is necessarily not naturally occurring. Accordingly, the claims are not directed to a judicial exception.
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.
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 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. 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 1-10 and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Broadbent et al. (WO 2020/100072).
Broadbent teaches that interactions between various microorganisms have been well characterized in number diverse environments and one example of a symbiotic relationship includes the production and secretion of metabolites by one organism that are utilized by another (p. 1, lines 15-23). Broadbent states that it would be “highly desirable” to be provided with means of increasing alcohol production during yeast fermentation that would exploit, rather than limit, the symbiotic relationship between yeasts and bacteria, especially lactic acid bacteria (p. 2, lines 8-10). Accordingly, Broadbent teaches a combination of a bacterial host cell and a yeast host cell exhibiting a symbiotic relationship to convert a first metabolic product into a second metabolic product (p. 1, lines 11-13). Broadbent teaches that the symbiotic combination achieves higher fermentation yields and, in some embodiments, provides higher robustness (p. 2, lines 11-18). The combination is a first microbial host cell having a first metabolic pathway comprising one or more first enzymes for producing a first metabolic product and a second microbial host cell having a second metabolic pathway comprising one or more second enzymes for converting at least in part the first metabolic product into a second metabolic product (p. 2, lines 19-23).
Regarding claim 1, Broadbent teaches the following.
With respect to a combination for making ethanol from a biomass comprising hexoses, the limitation “for making ethanol from a biomass comprising hexoses” is the intended use of the “combination” (MPEP § 2111.02). As discussed above, Broadbent teaches “a combination” and the intended use of the combination does not impart any particular structure on the combination. Accordingly, there is no requirement that Broadbent teaches that the combination is “for making ethanol from a biomass comprising hexoses”.
In the interest of compact prosecution, it is noted that Broadbent teaches that the second metabolic product is ethanol (p. 3, lines 15-16; p. 4, lines 22-23) and teaches processes for converting a biomass into a fermentation product and the process comprises contacting the biomass with the combination (p. 8, lines 14-21). Broadbent teaches that “[t]he biomass that can be fermented with the combination of host cells…includes any type of biomass known in the art” (p. 50, lines 8-9). Thus, Broadbent provides an invention concerned with making ethanol from a not particularly limited biomass.
With respect to a bacterial host cell, as discussed above, Broadbent teaches a combination comprising a first microbial host cell (p. 2, lines 19-23). Broadbent teaches that the first microbial host cell is a bacterial host cell (p. 2, lines 34-35).
With respect to the first metabolic pathway comprising one or more first polypeptides for converting acetate into ethanol, Broadbent provides a pathway in Figure 8 in which a metabolic product produced by the bacterial host cell (acetic acid; acetate) can be metabolized to ethanol by the yeast host cell (p. 142, lines 17-21; Figure 8, dotted line).
This pathway shows conversion of acetate into ethanol (through acetyl-CoA synthetase, acetylating acetaldehyde dehydrogenase, and alcohol dehydrogenase; Figure 8).
Broadbent’s teaching differs from the instant claim because it teaches that the yeast host cell, rather than the bacterial host cell possesses the first metabolic pathway comprising one or more first polypeptides for converting acetate into ethanol.
Nonetheless, it would have been obvious to have integrated the acetyl-CoA synthetase and acetylating acetaldehyde dehydrogenase into the bacterial host cell, rather than the yeast host cell. The claimed invention differs only in which component of the “combination” possesses the metabolic pathway for converting acetate into ethanol. Broadbent teaches that if the yeast host cell does not natively possess this activity, the yeast host cell can be genetically modified to provide or increase its ability to convert acetate to acetyl-CoA and acetyl-CoA into acetaldehyde (p. 14, line 17 through p. 15, line 2). Thus, a person having ordinary skill in the art would readily recognize that the heterologous enzymes could easily be inserted into the bacterium rather than the yeast. There would have been a reasonable expectation of success because:
(1) the claimed combination merely requires that the bacterial host cell has the pathway (i.e., does not require any particular effect);
(2) Broadbent teaches that the acetyl-CoA synthetase and acetylating acetaldehyde dehydrogenase enzymes can be from bacteria such as Bifidobacterium sp. or Saccharomyces sp., respectively (p. 28, lines 1-36). Accordingly, Broadbent envisions using bacterial enzymes in yeast, suggesting that the origin of the enzyme is not particularly relevant to expression of this system;
Moreover, it is noted that applicant’s disclosure provides evidence that bacterial hosts may natively possess such enzymes by teaching “…the polypeptide having acetyl-CoA synthetase (ACS) activity is native to the bacterial host cell” (p. 16, lines 4-5) and “in the bacterial host cell, the acetaldehyde dehydrogenase can be of prokaryotic or eukaryotic origin”, “can be native or heterologous to the bacterial host cell”, and can be obtained from Lactiplantibacillus such as L. pentosus (p. 18, lines 29-35). L. pentosus is one of the bacterial hosts taught by Broadbent (p. 40, lines 6-36). See also claim 3 which states that these components can be native to a bacterial host. Thus, there is a reasonable expectation that acetyl-CoA synthetase and acetylating acetaldehyde dehydrogenase would be functional in a bacterial host cell.
The modification merely requires using Broadbent’s known technique of providing a first metabolic pathway comprising one or more first polypeptides for converting acetate into ethanol to a bacterial, rather than yeast, host cell. And there would have been a predicable result of this substitution because Broadbent demonstrates throughout its disclosure that both yeast and bacterial hosts may possess heterologous polypeptides from the opposite kingdom. This obviousness is based upon the “Applying a Known Technique to a Known Device (Method, or Product) Ready for Improvement To Yield Predictable Results” rationale set forth in in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(D).
For at least this reason, Broadbent suggests a bacterial host cell with a first metabolic pathway comprising one or more first polypeptides for converting acetate into ethanol.
With respect to the second metabolic pathway comprising one or more second polypeptides for the conversion of glycerol into dihydroxyacetone-phosphate, Broadbent teaches that when the first metabolic product is a sugar alcohol such as glycerol, the second metabolic product can be ethanol and involved in the anabolism of dihydroxyacetone-phosphate (p. 48, lines 3-14). Broadbent teaches that the first metabolic product can be glycerol which can subsequently be metabolized to ethanol through the metabolic pathway of Figure 2 (p. 12, lines 32-36). Figure 2 (dashed lines) shows a pathway wherein glycerol can be converted into dihydroxyacetone-phosphate (through glycerol dehydrogenase and dihydroxyacetone kinase). Accordingly, Broadbent provides a bacterial host cell with a second metabolic pathway comprising one or more second polypeptides for the conversion of glycerol into dihydroxyacetone-phosphate.
With respect to the third metabolic pathway comprising one or more third heterologous polypeptides for converting pyruvate into ethanol, Broadbent teaches that the bacterial host cell can have native pyruvate decarboxylase activity or can be genetically modified to provide or increase pyruvate decarboxylase activity (p. 41, lines 31-35). Broadbent teaches that this can be done by introducing at least one copy of one or more heterologous nucleic acid molecules encoding a heterologous citrate lyase, a heterologous pyruvate decarboxylase, heterologous alcohol dehydrogenase, and/or heterologous oxaloacetate decarboxylase (p. 42, lines 25-32). Pyruvate decarboxylase is an enzyme catalyzing the decarboxylation of pyruvic acid (pyruvate) into acetaldehyde and carbon dioxide (p. 44, lines 28-29). To this end, Broadbent provides a third metabolic pathway wherein trehalose can be metabolized to ethanol by a bacterial host cell (shown in Figure 1). Figure 1 shows a pathway wherein pyruvate is converted to ethanol (through pyruvate decarboxylase and alcohol dehydrogenase). Broadbent states that this pathway (solid lines) “represent[s] metabolic reactions that occur in the yeast host cell and the bacterial host cell” (p. 8, lines 31-35).
According, Broadbent provides a bacterial host cell with a third metabolic pathway comprising one or more third heterologous polypeptides for converting pyruvate into ethanol.
With respect to the yeast host cell, Broadbent teaches a combination comprising a second microbial host cell (p. 2, lines 19-23). Broadbent teaches that the second microbial cell is a yeast host cell (p. 2, line 34 through p. 3, line 1).
With respect to the fourth metabolic pathway comprising one or more fourth polypeptides for producing glycerol, as discussed above, Broadbent provides many metabolic pathways. Broadbent teaches that Figure 2 shows a pathway identified by dotted lines used by the yeast host cell for glycerol production (p. 9, lines 3-9). Figure 2 (dotted lines) shows that dihydroxyacetone phosphate generated by the bacteria (dashed lines) is converted into glycerol by the yeast host cell (through dihyxroxyacteone-3-phosphate dehydrogenase and glycerol-phosphate phosphatase). Accordingly, Broadbent provides a yeast host cell with a fourth metabolic pathway comprising one or more fourth polypeptides for producing glycerol.
With respect to the fifth metabolic pathway comprising one or more fifth polypeptides for generating acetate, Broadbent teaches that the yeast host cell can be genetically modified to provide a secondary substrate to the bacterial host cell and this can be done by introducing one or more heterologous nucleic acid molecules encoding a NADP+-dependent aldehyde dehydrogenase and/or a phosphoketolase (p. 24, lines 5-18). This can also be done by introducing a strong promoter upstream of a native protein (Id.). Accordingly, Broadbent provides a yeast host cell with a fifth metabolic pathway comprising one or more fifth polypeptides for generating acetate. The position that Broadbent’s NADP+-dependent aldehyde dehydrogenase and/or a phosphoketolase are part of a fifth metabolic pathway is supported by applicant’s disclosure which states that in some embodiments, the one or more fifth polypeptides for generating acetate comprises one or more native or heterologous polypeptides having phosphoketolase activity (p. 3, lines 23-25).
For at least these reasons, Broadbent renders obvious the claimed combination of claim 1.
Regarding claim 2, as discussed above, the phrase “for making ethanol from a biomass comprising hexoses” is the intended use of the “combination” of claim 1. Accordingly, the type of biomass does not impart any meaningful structural limitations on the claimed invention because there is no requirement that the composition comprise a biomass, let alone a biomass comprising or derived from corn. Thus, for the reasons discussed above, claim 2 is obvious over Broadbent.
Nonetheless, in the interest of compact prosecution, it is noted that Broadbent teaches that the biomass can be any type of biomass and may include corn mashes, corn cobs, or corn (i.e., a biomass comprising or derived from corn)(p. 50, lines 8-12 and 27-36; p. 51, lines 13-18).
Regarding claim 3, as discussed above, Broadbent provides a pathway in Figure 8 in which a first metabolic product produced by the bacterial host cell (acetate) can be metabolized to ethanol by the bacterial host cell (p. 142, lines 17-21; Figure 8). This pathway shows conversion of acetate into ethanol (through acetyl-CoA synthetase, acetylating acetaldehyde dehydrogenase, and alcohol dehydrogenase; Figure 8). For the reasons discussed above, it would have been obvious to have arrived at a bacterial host cell possessing these enzymes.
Acetyl-CoA synthetase is a “one or more native or heterologous enzymes for converting acetate into acetyl-coA”. Acetylating acetaldehyde dehydrogenase is “one or more native or heterologous enzymes for converting acetyl-CoA into acetaldehyde. Although the “optional” limitation is not required by the claim, it is noted that Broadbent contemplates the use of bi-functional acetaldehyde/alcohol dehydrogenases (p. 39, lines 1-8).
Regarding claim 4, as discussed above, Broadbent renders obvious the use of an acetyl-CoA synthetase in the bacterial host cell. Broadbent teaches that the acetyl-CoA synthetase can be, for example, ACS2 (i.e., a polypeptide having acetyl CoA-synthetase (ACS) activity)(p. 28, lines 22-36). As discussed above, Broadbent also teaches a polypeptide having acetaldehyde-dehydrogenase (AADH) activity, a polypeptide having an alcohol dehydrogenase (ADH) activity, and a polypeptide having a bifunctional acetaldehyde/alcohol dehydrogenase (ADHE) activity.
Regarding claim 5, the intended use of the pathway is “for the dehydrogenation of glycerol”. This limitation imparts a structure. The structure is that the pathway must be capable of dehydrogenation of glycerol.
As discussed above, Broadbent provides a second pathway in Figure 2 (dashed lines) which shows glycerol can be converted into dihydroxyacetone-phosphate (through glycerol dehydrogenase and dihydroxyacetone kinase). Thus, Broadbent’s second metabolic pathway is for the dehydrogenation of glycerol.
Regarding claim 6, as discussed above, Broadbent provides a pathway which uses glycerol dehydrogenase and dihydroxyacetone kinase. Broadbent teaches that the bacterial host can be selected based on its native ability to convert glycerol into dihydroxyacetone and dihydroxyacetone into dihydroxyacetone-phosphate or can be genetically modified to provide or increase its ability to perform this function (p. 13, lines 1-18). Thus, Broadbent provides one or more second polypeptides which comprise a native or heterologous polypeptide having glycerol dehydrogenase (GLDA) activity or a combination of the native and the heterologous polypeptides having GLDA activity and a native or heterologous polypeptide having an ATP-dependent dihydroxyacetone kinase (DAK) activity).
Regarding claim 7, as discussed above, Broadbent teaches that the bacterial host cell can have native pyruvate decarboxylase activity or can be genetically modified to provide or increase pyruvate decarboxylase activity (p. 41, lines 31-35). Broadbent teaches that this can be done by introducing at least one copy of one or more heterologous nucleic acid molecules encoding a heterologous citrate lyase, a heterologous pyruvate decarboxylase, heterologous alcohol dehydrogenase, and/or heterologous oxaloacetate decarboxylase (p. 42, lines 25-32). Broadbent states that this pathway (solid lines) “represent[s] metabolic reactions that occur in the yeast host cell and the bacterial host cell” (p. 8, lines 31-35).
Accordingly, Broadbent provides one or more third heterologous polypeptides which comprise a native or heterologous polypeptide having pyruvate decarboxylase (PDC) activity and a native or heterologous polypeptide having alcohol dehydrogenase (ADH) activity).
Regarding claim 8, Broadbent teaches that the host cell is a lactic acid bacterium and this encompasses but is not limited to genera such as Lactobacillus, Leuconostoc, Pediococcus, etc. (p. 40, line 6 through p. 41, line 6).
Regarding claim 9, Broadbent teaches that the host cell can be L. plantarum (a species falling in Lactiplantibacillus sp.) or L. casei (a species falling in Lacticaseibacillus sp.)(Id.).
Regarding claim 10, Broadbent teaches that the bacterial host can be modified as to decrease its lactate dehydrogenase activity and can have at least one inactivated native gene coding for a lactate dehydrogenase (p. 5, lines 1-7; p. 48, lines 22-24).
Regarding claim 13, Broadbent teaches that Figure 2 shows a pathway identified by dotted lines used by the yeast host cell for glycerol production (p. 9, lines 3-9). Figure 2 (dotted lines) shows that dihydroxyacetone phosphate generated by the bacteria (dashed lines) is converted into glycerol by the yeast host cell (through dihydroxyacteone-3-phosphate dehydrogenase and glycerol-phosphate phosphatase). Broadbent also teaches that when the carbohydrate is glycerol, the yeast may possess a glycerol-3-phopshphate dehydrogenase pathway and in such embodiments comprises a glycerol kinase or a glycerol-3-phosphate dehydrogenase (p. 7, lines 9-20).
Thus, Broadbent teaches one or more fourth polypeptides which comprise a native or heterologous polypeptide having glycerol-3 phosphate dehydrogenase or phosphatase activity.
Regarding claim 14, as discussed above, Broadbent teaches that the yeast host cell can be genetically modified to provide a secondary substrate to the bacterial host cell and this can be done by introducing one or more heterologous nucleic acid molecules encoding a NADP+-dependent aldehyde dehydrogenase and/or a phosphoketolase (p. 24, lines 5-18). This can also be done by introducing a strong promoter upstream of a native protein (Id.). Broadbent teaches that the phosphoketolase can be single-specificity or dual-specificity (p. 24, lines 25-35).
Thus, Broadbent teaches one or more fifth polypeptides for generating acetate which comprise one or more native or heterologous polypeptides having phosphoketolase activity which has single specificity or dual specificity.
Regarding claim 15, Broadbent teaches that the yeast host cell can be from Saccharomyces sp. (p. 7, lines 21-23).
Regarding claim 16, for the reasons discussed above, Broadbent renders obvious a bacterial host cell comprising each of the recited metabolic pathways.
Regarding claim 17, as discussed above, Broadbent teaches that the composition may comprise the combination and a biomass such as corn. Biomasses such as corn are necessarily “a biomass comprising hexoses”. This position is supported by applicant’s specification which states that “[t]he biomass comprises hexoses, which include but are not limited to, glucose” and “[t]he biomass can comprise or be derived from starch (which can be…provided from corn)” (p. 49, line 33 through p. 50, line 4).
Claims 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Broadbent et al. (WO 2020/100072) in view of Fox et al. (Current Opinion in Chemical Engineering, 2020, vol. 30, pages 9-16).
The teachings of Broadbent are set forth above and applied herein. Broadbent is found to render obvious claims 1-10 and 13-17.
Regarding claims 11-12, as discussed above, Broadbent provides a combination of a yeast and a bacterial cell which is used for the production of ethanol.
Broadbent provides many metabolic pathways possessed by the bacterial host cell but does not teach that the bacterial host cell has a genetic modification for reducing carbon catabolite repression or for decreasing the expression or inactivating at least one gene encoding a polypeptide involved in glycolytic flux.
Nonetheless, Fox et al. reviews genetically modified bacterial cells such as Escherichia coli (abstract). Specifically, Fox teaches that the economic efficacy and sustainability of bioprocessing is partially dependent on the ability to utilize waste materials containing sugars and other carbon sources as a feedstock (p. 9, left col., par. 1). Fox states that E. coli is a model organism commonly used for bioprocessing which can be genetically altered using metabolic engineering techniques to produce value-added products (Id.). Raw biomass is composed of cellulose, hemicellulose and pectin which have subunits of multiple different sugars and sugar acids and technologies for the breakdown of these complex polymers have been studied intensively (p. 9, left col., par. 1 through right col., par. 1). Fox teaches that diverse feeds causes a problem of carbon catabolite repression which is an intrinsic substrate preference mechanism found in many organisms and metabolic engineers have a vested interest in developing methods to alleviate the effects of CCR and allow for non-discriminatory sugar utilization due to the large potential of engineered systems with mixed sugar feedstocks (p. 9, right col., par. 1). Fox teaches that CCR is primarily realized through the phosphoenolpyruvate transferase system (PTS) (p. 9, right col., par. 2). The most common modification made to the PTS is to generate a strain with a ΔptsG mutation and this strategy has been shown to increase titers of hydrogen, ribose, xylonate and many other products from feedstocks of mixed sugars due to increased secondary sugar uptake and this change leads to a slow growth and low glucose utilization phenotype (p. 10, right col., par. 3). This modification also has been postulated to increase phosphoenolpyruvate (PEP) availability (Id.). Another solution is to co-culture strains with limited glucose consumption due to a PTS mutation with strains that can efficiently utilize glucose but cannot consumer the secondary sugar and such methods have been used to generate ethanol and butanol in a consortium (p. 12, left col., par. 2).
Accordingly, because Broadbent teaches a combination of yeast and bacteria for the purpose of generating metabolites such as ethanol, it would have been obvious to have applied Fox’s known technique of decreasing the expression or inactivating a gene encoding a PTS transporter in the bacterial host cell. There would have been a predictable result because Fox teaches:
That this method has been used previously when co-culturing bacteria with Saccharomyces to produce ethanol and butanol; and
Because Fox teaches that this modification increases PEP availability, which is directly upstream of ethanol (as demonstrated by the metabolic pathways shown in Figures 1-4 and 8 of Broadbent).
This obviousness is based upon the “Applying a Known Technique to a Known Device (Method, or Product) Ready for Improvement To Yield Predictable Results” rationale set forth in in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(D).
Thus, claims 11-12 are obvious over Broadbent in view of Fox.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-10 and 13-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/537,410 in view of Broadbent et al. (WO 2020/100072); claims 11-12 are provisionally rejected over the same and further in view of Fox et al. (Current Opinion in Chemical Engineering, 2020, vol. 30, pages 9-16).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 1, as discussed above, the phrase “for making ethanol from a biomass comprising hexoses” is the intended use of the composition. Claim 1 of ‘410 requires a bacterial host cell which has a first metabolic pathway comprising one or more first polypeptides for converting acetate into ethanol, a second metabolic pathway comprising one or more second polypeptides for converting glycerol into dihydroxyacetone phosphate, and a third metabolic pathway comprising one or more third polypeptides for converting pyruvate into ethanol. Moreover, Claim 1 of ‘410 requires a yeast host cell with a fourth metabolic pathway comprising one or more fourth polypeptides for producing glycerol. The claims differ in that the composition of claim 1 of ‘410 does not require a fifth metabolic pathway for generating acetate.
Nonetheless, Broadbent teaches that when the metabolism of the first metabolic product is oxidative, such as generating mannitol, sorbitol, or glycerol, the yeast host cell can provide a secondary substrate that could act as an electron acceptor and allow redox balance (p. 24, lines 5-18). Broadbent teaches that the yeast host cell can be genetically modified to provide a secondary substrate to the bacterial host cell and this can be done by introducing one or more heterologous nucleic acid molecules encoding a NADP+-dependent aldehyde dehydrogenase and/or a phosphoketolase (p. 24, lines 5-18). This can also be done by introducing a strong promoter upstream of a native protein (Id.).
Therefore, it would have been obvious to have modified the yeast host cell of ‘410 such that it had the above modification because the yeast host cell of ‘410 and the instant application produce glycerol and Broadbent teaches that it would be useful to make the above modification in that case.
Regarding claim 2, as discussed above, this claim only limits the composition of the intended use. Accordingly, for the reasons discussed above, the claim is unpatentable over ‘410 in view of Broadbent.
Regarding claims 3-4, these claims overlap in scope with claims 3-4 of ‘410.
Regarding claims 5-8, these claims are the same as claims 5-8 of ‘410.
Regarding claim 9, this claim overlaps in scope with claim 9 of ‘410.
Regarding claim 10, this claim is the same as claim 10 of ‘410.
Regarding claims 11-12, as discussed above, ‘410 in view of Broadbent renders obvious the combination of claim 1. The instant claims differ because neither the claims of ‘410 nor Broadbent teach reducing carbon catabolite repression or decreasing expression of a gene encoding a polypeptide involved in a glycolytic flux.
Nonetheless, Fox et al. reviews genetically modified bacterial cells such as Escherichia coli (abstract). Specifically, Fox teaches that the economic efficacy and sustainability of bioprocessing is partially dependent on the ability to utilize waste materials containing sugars and other carbon sources as a feedstock (p. 9, left col., par. 1). Fox states that E. coli is a model organism commonly used for bioprocessing which can be genetically altered using metabolic engineering techniques to produce value-added products (Id.). Raw biomass is composed of cellulose, hemicellulose and pectin which have subunits of multiple different sugars and sugar acids and technologies for the breakdown of these complex polymers have been studied intensively (p. 9, left col., par. 1 through right col., par. 1). Fox teaches that diverse feeds causes a problem of carbon catabolite repression which is an intrinsic substrate preference mechanism found in many organisms and metabolic engineers have a vested interest in developing methods to alleviate the effects of CCR and allow for non-discriminatory sugar utilization due to the large potential of engineered systems with mixed sugar feedstocks (p. 9, right col., par. 1). Fox teaches that CCR is primarily realized through the phosphoenolpyruvate transferase system (PTS) (p. 9, right col., par. 2). The most common modification made to the PTS is to generate a strain with a ΔptsG mutation and this strategy has been shown to increase titers of hydrogen, ribose, xylonate and many other products from feedstocks of mixed sugars due to increased secondary sugar uptake and this change leads to a slow growth and low glucose utilization phenotype (p. 10, right col., par. 3). This modification also has been postulated to increase phosphoenolpyruvate (PEP) availability (Id.). Another solution is to co-culture strains with limited glucose consumption due to a PTS mutation with strains that can efficiently utilize glucose but cannot consumer the secondary sugar and such methods have been used to generate ethanol and butanol in a consortium (p. 12, left col., par. 2).
Accordingly, because ‘410 and Broadbent teach a combination of yeast and bacteria for the purpose of generating metabolites such as ethanol, it would have been obvious to have applied Fox’s known technique of decreasing the expression or inactivating a gene encoding a PTS transporter in the bacterial host cell. There would have been a predictable result because Fox teaches:
That this method has been used previously when co-culturing bacteria with Saccharomyces to produce ethanol and butanol; and
Because Fox teaches that this modification increases PEP availability, which is directly upstream of ethanol (as demonstrated by the metabolic pathways shown in Figures 1-4 and 8 of Broadbent).
Thus, claims 11-12 are obvious over ‘410 in view of Broadbent and Fox.
Regarding claim 13, this claim is the same as claim 11 of ‘410.
Regarding claim 14, as discussed above, Broadbent renders obvious a yeast host cell with one or more native or heterologous polypeptides having phosphoketolase activity.
Regarding claim 15, this claim is the same as claim 13 of ‘410.
Regarding claim 16, this claim overlaps with claim 14 of ‘410.
Regarding claim 17, although ‘410 is directed to a combination of the yeast and bacterial host cell with a biomass comprising pentoses, ‘410’s specification teaches that biomasses containing pentose include inter alia corn and corn mash ([0145], [0147], [0159]). Because “biomass comprising hexoses” also includes corn and corn mash, the claim is obvious over ‘410 in view of Broadbent for the reasons discussed above in claim 1.
Claims 1-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/967,018.
This is a provisional nonstatutory double patenting rejection.
The claims of ‘018 are generically directed to a combination of a first and second microbial host cell wherein the second microbial host at least in part converts a first metabolic product into a second metabolic product. ‘018 requires that the first or second microbial host cell is a bacterial host cell or a yeast host cell. Claim 8 of ‘018 limits one of the metabolic products to be ethanol. Because each of the claims of the present application require these components, the claims overlap in scope.
Conclusion
No claim is allowed.
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/GRANT C CURRENS/Examiner, Art Unit 1651
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