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
Application Status
This application is a DIV of US patent application 16/664,549, filed on 05/20/2022.
Claims 1-2, 4, 8, 12, 16, 20-21, 42-44, 45-47, 50, and 136-138 are currently pending in this patent application.
In response to a previous Office action, a Non-Final Rejection Office action (mailed on 06/27/2025), Applicants filed a response and an amendment on 09/29/2025, amending claim 1 is acknowledged.
Claims 45-47, and 50, remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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, 2, 4, 8, 12, 16, 20, 21, 42-44 and 136-138 are present for examination.
Applicants' arguments filed on 09/029/2025, have been fully considered and are deemed persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
New-Claim Rejections – AIA 35 U.S.C. § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negative by the manner in which the invention was made.
According to MPEP 2143:
“Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield
predictable results;
(B) Simple substitution of one known element for another to obtain predictable
results;
(C) Use of known technique to improve similar devices (methods, or products)
in the same way;
(D) Applying a known technique to a known device (method, or product) ready
for improvement to yield predictable results;
(E) “ Obvious to try ” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in
either the same field or a different one based on design incentives or other market
forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art
reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.”
Claims 1, 2, 4, 8, 12, 16, 20, 21, and 42-44 are under 35 U.S.C. 103(a) before the effective filing date as being unpatentable over Osterhout et al. Microorganisms and methods for the biosynthesis of aromatics, 2,4-pentadienoate and 1,3-butadiene, US 2012/0021478 A1, publication 01/26/2012, see IDS), in view of Adkins et al. (Engineering microbial chemical factories to produce renewable “bio-monomers”. Frontiers In Microbiology, (2012), 3: Article, 313: Pg. 1-12), Dauner et al. (Recombinant host cells comprising phosphoketolase, US 2012/0156735, A1, publication 6/21/2012, claim priority of 61/356,379, filed on 06/18/2010, see IDS), Burgard et al. (Microorganisms and methods for producing butadiene and related compounds by formate assimilation. WO 2014/152434 A2, publication 09/25/2014, claim benefit of 61/799,255, filed on 03/15/2013, see IDS), and Marrs et al. (Reducing carbon dioxide production and increasing ethanol yield during microbial ethanol fermentation. WO 2010/104938 A1, publication 09/16/2010), which is also published as US 2014/0106424 A1, publication 04/17/2014, claim benefit of 61/158,881, filed on 03/10/2009, see IDS, which will be used to identify claim limitations).
The Broadest Reasonable Interpretation (BRI) of claim 1, which is drawn to any non-naturally occurring microbial organism, said microbial organism having a butadiene pathway and comprising at least one exogenous nucleic acid encoding a butadiene pathway enzyme expressed in a sufficient amount to produce butadiene from acetyl-CoA via malonyl-CoA and 3-oxoglutaryl-CoA, , i.e. only two enzyme needs to be exogenous and other enzymes could be endogenous, wherein said butadiene pathway comprises a pathway of: (17) 2A, 2B, and 2C, wherein 2A is an acetyl-CoA carboxylase; 2B is a malonyl-CoA: acetyl-CoA acyltransferase; 2C is a 3-oxoglutaryl-CoA reductase (ketone reducing).
Regarding claims 1-2, 4, 8, 12, 16, 20-21, 42-43 and 44, Osterhout et al. teach a non-naturally occurring microbial organism including E. coli, wherein the microbial organism having a butadiene pathway and comprising at least one exogenous nucleic acid encoding a 1,3-butadiene pathway enzymes, wherein the pathway enzyme expressed in a sufficient amount to produce butadiene (para [0242]), wherein said butadiene pathway comprises enzymes including a malonyl-CoA: acetyl-CoA acyltransferase, 3-oxoglutaryl-CoA reductase (ketone forming) and pentadienoate decarboxylase of 2B, 2C and 2I of instant application respectively (see, Fig. 21, see, SnagIt image below, and para [0036], [0081]-[0082], [0191], [0242], [0243], [0247], [0248], [0253], and [0254]), wherein said microbial organism also comprises acetate kinase, phosphotransacetylase and acetyl-CoA synthetase as claimed in claim 4 (see, para 230), and methanol methyltransferase as claimed in claim12 (see, para 508, and Table 1), as well as said non-natural microbial organism also comprises formate dehydrogenase (3S), and pyruvate ferredoxin oxidoreductase (3R) as claimed in claim 20 (see, para 229, 233, and claim 216), wherein said microbial organism also comprise hydrogenase as claimed in claim 21 (see, claim 196, 199, and 216) 2 (see, Fig. 4, para [0019], [0043], [0081], [0171], [0191]-[0192]), wherein said non-natural microbial organism host cell is a bacteria including E. coli (para [0171]), comprises at least one or two exogenous nucleic acids, wherein at least one exogenous nucleic acid is heterologous, where the culturing condition is substantially anaerobic (see, para [0064], [0076], [0077], [0078], [0081-0082], [0191]-[0192], and claims 1, 46-50, 54, 177, 193, 196, 200, 213 and 216). Osterhout et al. further teach expression of genes encoding enzymes of formaldehyde fixation pathway utilizing enzymes including dihydroacetone synthase (3D) as claimed in claim 8 (see, para 396), although, Osterhout et al. do not teach formaldehyde fixation pathway. In addition, Osterhout et al. teach expression of genes encoding enzymes including methanol methyltransferase (4A) and methylenetetrahydrofolate dehydrogenase (4C) (see, para 229, and 508, Table 1) of methanol metabolic pathway as claimed in claim 12 (see, para 396).
Claim 16 is included in this rejection because claim 16 requires formate reductase enzyme for expression (1) 3E, wherein the synonym of formate reductase is formate dehydrogenase (see, KEGG Enzyme as evidence), which is taught by Osterhout et al. (see, para 229).
Osterhout et al. do not teach expression of genes encoding enzymes for formaldehyde fixation pathway as claimed in claim 8, and do not teach expression of fructose 6-phosphate phosphoketolase (3T) or xylulose -5-phosphate phosphoketolase (3U), and Osterhout et al. do not teach acetyl-CoA carboxylase enzyme (for claim 1).
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However, Adkins et al. teach engineering microbial chemical factories to produce renewable bio-monomers including butadiene as claimed from acetyl-CoA via malonyl CoA in a recombinant Corynebacterium glutamicum and E. coli cell platform and further teach overexpression exogenous acetyl-CoA carboxylase gene encoding enzyme in recombinant host cells capable of producing more malonyl-CoA to divert malonyl-CoA as substrate to produce 3-oxo-glutaryl-CoA, which will accelerate the energy flow towards the production of 1,4-butadiene, a polyvinyl building blocks for industrial purpose (see, abstract, pg7, right Col, para 3, pg9, left Col, para 2, Fig. 2, and 6).
Adkins et al. do not teach expression of genes encoding enzymes for formaldehyde fixation pathway as claimed in claim 8, and do not teach expression of fructose 6-phosphate phosphoketolase (3T) or xylulose -5-phosphate phosphoketolase (3U).
However, Dauner et al. teach said organisms comprising pathways (1) and (3) fructose-6-phosphate/ xylose-5-phosphate phosphoketolase and phosphotransacetylase (para [0071]). Dauner et al. also teach a xylulose-5-phosphate/ fructose-6-phosphate phosphoketolase, which is expressed in host cells (para [0196] and causes increased production of the products (para 0159]), and the expression of a polypeptide phosphotransacetylase activity can catalyzes the conversion of acetyl-phosphate into acetyl-CoA. Based on Dauner et al. teaching, before, the effective filing date, it would have been obvious to one of a skilled artisan to include nucleic acid encoding xylulose-5-phosphate/ fructose 6-phosphate phosphoketolase and phosphotransacetylase of Dauner et al. in the organisms of Osterhout et al. and modify Osterhout et al. in view of the teachings of Dauner et al. to arrive the claimed invention because said enzymes increase the production of butadiene, an expensive chemical, which is financially beneficial.
Regarding claims 8, Osterhout et al. nor Adkins et al., Dauner et al. do not teach formaldehyde fixation pathway in said host cell. Regarding claims 12, 16, 20 and 21, Osterhout et al. do not teach methanol metabolic pathway (for claim 12) including expression of methanol dehydrogenase (4J), methanol methyl transferase (4A) or methylenetetrahydrofolate reductase (4B), formate assimilation pathway (for claims 16 and 20), and methanol oxidative pathway (for claim 21) including expression of methanol dehydrogenase (3A), and carbon monoxide dehydrogenase or hydrogenase.
However, Burgard et al. teach a non-naturally occurring microbial organism host E. coli having a methanol metabolic pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a methanol metabolic pathway enzymes (see, abstract, pg 2, 8-9, 10, and Fig. 3) expressed in a sufficient amount to produce pyruvate, wherein said formaldehyde fixation or assimilation pathway comprises a 3-hexulose-6-phosphate synthase (3B) (see, pg 8-9, 10, 58, 59, 61,Example III, and claims 1, 6, 8, 17, 20, 93, 96, 98, 125, 170, 173, 175, 220 and 226), and 6-phospho-3-hexuloisomerase (3C) (see, claims 17, 91 and 123), and a dihydroxyacetone synthase (3D), (see, claims 1, 6, 8, 17, 20, 93, 96, 98, 125, 170, 173, 175, 220 and 226). Based on Burgard et al. teaching, before, the effective filing date, it would have been obvious to one of a skilled artisan to include nucleic acid encoding a 3-hexulose-6-phosphate synthase (3B) (see, claim 17, 91 and 123), 6-phospho-3-hexuloisomerase (3C) (see, claims 1, 6, 8, 17, 20, 93, 96, 98, 125, 170, 173, 175, 220 and 226), and a dihydroxyacetone synthase (3D), (see, claims 1, 6, 8, 17, 20, 93, 96, 98, 125, 170, 173, 175, 220 and 226) of formaldehyde fixation pathway of Burgard et al. in the organisms of Osterhout et al. and modify Osterhout et al. in view of the teachings of Burgard et al. to arrive the claimed invention because said enzymes increase the production of pyruvate, a precursor of butadiene, an expensive chemical, which is financially beneficial.. Based on Burgard et al. teaching, before, the effective filing date, it would have been obvious to one of a skilled artisan to include nucleic acid encoding a methanol dehydrogenase of methanol metabolic and methanol oxidation pathway of Burgard et al. in the organisms of Osterhout et al. and modify Osterhout et al. in view of the teachings of Burgard et al. to arrive the claimed invention because said enzymes increase the production of butadiene, an expensive chemical, which is financially beneficial.
Regarding claims 16, and 20, Osterhout et al. do not teach formate assimilation pathway (for claims 16 and 20) including expression of formate reductase (3E) and pyruvate formate lyase (3Q).
However, Marrs et al. teach a recombinant microbial organism host including E. coli or S. cerevisiae (Example 3), wherein said organism comprises at least one exogenous nucleic acid encoding a formate reductase and pyruvate formate lyase enzyme, expressed in a sufficient amount to produce formaldehyde from formate, the precursors of butadiene (see, (para [0020]-[0021], [0152] and Fig. 4-6).
Claims 42-44 are included in this rejection because only one gene is required for exogenous gene, which is heterologous, host cell is E. coli bacteria and culture condition is substantially anaerobic (see, para 82, , which were taught by Osterhout et al.
Based on the teachings of Osterhout et al., Adkins et al., Dauner et al., Burgard et al., and Mars et al. et al., before, the effective filing date of the claimed invention, it would have been obvious to one of a skilled artisan to include acetyl-CoA carboxylase to produce increase amount malonyl-CoA as taught by Adkins et al.; using nucleic acid encoding xylulose-5-phosphate/ fructose 6-phosphate phosphoketolase and phosphotransacetylase, nucleic acid encoding xylulose-5-phosphate/ fructose 6-phosphate phosphoketolase and phosphotransacetylase of Dauner et al. in the organisms of Osterhout et al. and modify Osterhout et al. in view of the teachings of Adkins et al. and Dauner et al. to arrive the claimed invention because said enzymes increase the production of butadiene, an expensive chemical, which is financially beneficial.
Conclusion
Status of the claims:
Claims 136-138 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 1, 2, 4, 8, 12, 16, 20, 21, and 42-44 stand rejected.
Applicant's amendments (see, substantial amendment of claim 1), necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Iqbal H Chowdhury whose telephone number is (571)272-8137. The examiner can normally be reached on 9 am to 5 pm Monday thru Friday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Iqbal H. Chowdhury, Primary Examiner
Art Unit 1656 (Recombinant Enzymes & Protein Crystallography)
US Patent and Trademark Office
Ph. (571)-272-8137 and Fax (571)-273-8137
/IQBAL H CHOWDHURY/
Primary Examiner, Art Unit 1656