DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s preliminary amendment to the claims, filed July 28, 2026, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Claims 1-3, 5, 7, and 10-12 are pending in the application.
Priority
This application is filed under 35 U.S.C. 371 as a national stage of international application PCT/EP2022/085917, filed December 14, 2022, which claims foreign priority under 35 U.S.C. 119(a-d) to European application no. 21215759.8, filed December 17, 2021. A certified copy of the foreign priority application has been filed in this application on June 11, 2024.
Restriction/Election
Applicant's election with traverse of Group I, pending claims 1-3, 5, 10, and 11 in the reply filed on July 28, 2026 is acknowledged. The traversal is on the ground that in view of applicant’s instant amendment to the claims, the inventions of Groups I and II now share the same or corresponding technical feature, which is a contribution over the prior art. This is not found persuasive because at least for the reasons set forth in the rejection under 35 U.S.C. 103, the technical feature of Group I is not a contribution over the prior art.
The requirement is still deemed proper and is therefore made FINAL.
Claims 7 and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 11, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Claim Objections
Claim 5 is objected to because of the following informalities:
Claim 5 is objected to in the recitation of “OaB” in line 1 and in the interest of improving claim form and improving consistency with claims 1, 3, and 11, it is suggested that “OaB” be replaced with “oAB.”
Claim 5 is also objected to in the recitation of “wherein one of more cells of the Corynebacterium genus differ from the wild type at least in the following features” and in the interest of improving claim form and consistency, it is suggested that the noted phrase be amended to recite (with markings to show changes made) “wherein the strainCorynebacterium genus differs from the wild type at least in the following features.”
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1-3, 5, 10 and 11 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.
Claims 1, 2 (claim 3 dependent therefrom), 5 (claim 11 dependent therefrom), and 10 are indefinite in the recitation of “by weight” because it is unclear as to what “weight” is being referenced. For example, “by weight” can be interpreted as referring to the weight of the entire culture medium or the weight of one component or a subcombination of components of the culture medium. In the interest of advancing prosecution, it is suggested that applicant clarify the meaning of “by weight” in the context of the claims.
Claims 1, 2 (claim 3 dependent therefrom), 5 (claim 11 dependent therefrom), and 10 are indefinite in the recitation of “the proportions of glucose and xylose add up to 100%” (claims 1 and 5) and “contributes the proportion lacking from 100%” (claims 2 and 10) because the claims recite percentages of glucose and xylose – not proportions. In the interest of advancing prosecution, applicant may consider amending claims 1 and 5 to replace “proportions” with “percentages” and amending claims 2 and 10 to replace “proportion” with “percentage.”
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.
Claims 1-3, 5, 10, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Jaeger et al. (WO 2015/124687 A1; cited on the IDS filed June 11, 2024; hereafter “Jaeger”) in view of Yamada et al. (EP 3061828 B1; cited on the IDS filed June 11, 2024; hereafter “Yamada”).
Claims 1-3 are drawn to a method of producing ortho-aminobenzoic acid (oAB) comprising culturing one or more cells of the Corynebacterium genus that are able to convert glucose and xylose to oAB in a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight,
wherein the proportions of glucose and xylose add up to 100%;
wherein oAB is produced; and
wherein said cells differ from the wild type at least in the following features:
(i) reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity;
(ii) elevated activity of shikimate kinase;
(iii) elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase;
(iv) presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase; and
(v) elevated activity of xylose isomerase and of xylulokinase.
Claims 5, 10, and 11 are drawn to a method of producing OaB comprising microbial fermentation of a strain of the Corynebacterium genus with a mixture of glucose and xylose as energy source and carbon source,
wherein one of more cells of the Corynebacterium genus differ from the wild type at least in the following features:
(i) reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity;
(ii) elevated activity of shikimate kinase;
(iii) elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase;
(iv) presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase; and
(v) elevated activity of xylose isomerase and of xylulokinase; and
wherein the mixture of glucose and xylose has a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight, and wherein the proportions of glucose and xylose add up to 100%.
Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18).
Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated expression of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
The differences between Jaeger and the claimed invention are:
While Jaeger teaches glucose and xylose as fermentable carbon substrates (p. 20, lines 24-27), Jaeger does not teach the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
While Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway (p. 4, lines 20-23), Jaeger does not teach elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
While Jaeger teaches xylose as a fermentable carbon substrate (p. 20, lines 24-27), Jaeger does not teach elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
Jaeger does not teach carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the culture medium of the o-aminobenzoate production method of Jaeger to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding difference 2), Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of Jaeger by deleting the tyrR gene. One would have been motivated and would have expected success because Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 3), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of Jaeger by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because Jaeger teaches xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 4), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of Jaeger modified according to Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the method of Jaeger modified according to Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the method of Jaeger modified according to Yamada. See MPEP 2112.IV and 2112.V.
Therefore, the methods of claims 1-3, 5, 10, and 11 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim Rejections - 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.
U.S. Patent No. 10,173,969 B2
Claims 1-3, 5, 10, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, 27, 28, 31, and 32 of U.S. Patent No. 10,173,969 B2 (cited on the attached Form PTO-892) in view of Jaeger and Yamada.
Claim 1 of the patent recites a method for producing aniline, comprising:
a) providing an aqueous solution of o-aminobenzoate, wherein said o-aminobenzoate comprises anthranilate anion and NH4 + and/or Na+ as cation,
b) converting said anthranilate anion to aniline by thermal decarboxylation in the presence or absence of a catalyst, and either
c1) purifying the aniline produced in step b) by distillation if the content of aniline in the aqueous solution obtained in method step b) is above 120 g/l, or
c2) extracting the aniline obtained in method step b) at least once in an organic solvent before purifying the aniline by distillation if the content of aniline in the aqueous solution obtained in method step b) is not more than 120 g/l;
claim 10 of the patent recites wherein said o-aminobenzoate is produced biologically by fermentation of a raw material comprising at least one fermentable carbon substrate using a recombinant microbial host cell capable of converting said raw material comprising a fermentable carbon substrate to o-aminobenzoate by fermentation;
claim 27 of the patent recites (in relevant part) wherein said fermentable carbon substrate comprises a C-5 monosaccharide comprising xylose;
claim 28 of the patent recites (in relevant part) wherein said fermentable carbon substrate comprises a C-6 monosaccharide comprising glucose;
claim 31 of the patent recites (in relevant part) wherein said recombinant host comprises a Corynabacterium strain; and
claim 32 of the patent recites wherein said bacteria comprises a Corynabacterium strain comprising Corynabacterium glutamincum.
The differences between the claims of the patent and the claims of this application are:
While the claims of the patent recite glucose and xylose as fermentable carbon sources for the production of o-aminobenzoate, the claims of the patent do not recite the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the patent do not recite reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the patent do not recite presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase as recited in claims 1 and 5;
While the claims of the patent recite xylose as a fermentable carbon source for the production of o-aminobenzoate, the claims of the patent do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the patent do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon substrate of the o-aminobenzoate production method of the claims of the patent to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the patent recite glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2), 3), and 5), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the patent recite biological production of o-aminobenzoate by fermentation using a C. glutamicum and Jaeger teaches reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 4), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the patent recite biological production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 6), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because the claims of the patent recite xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 7), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the patent modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the patent modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the patent modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 1, 10, 27, 28, and 31 of the patent.
U.S. Patent No. 10,731,187 B2
Claims 1-3, 5, 10, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 19, and 20 of U.S. Patent No. 10,731,187 B2 (cited on the attached Form PTO-892) in view of Jaeger and Yamada.
Claim 5 of the patent recites a method for producing aniline, the method comprising:
a) producing o-aminobenzoate by fermentation of a raw material comprising at least one fermentable carbon substrate using the recombinant microbial host cell of claim 1, wherein said o-aminobenzoate comprises an anthranilate anion,
b) converting said o-aminobenzoate from said anthranilate anion to anthranilic acid by acid protonation,
c) recovering said anthranilic acid by precipitation or by dissolving in an organic solvent, and
d) converting said anthranilic acid to aniline by thermal decarboxylation in an organic solvent,
claim 1 of the patent recites a recombinant microbial host cell capable of converting a raw material comprising a fermentable carbon substrate to o-aminobenzoate biologically,
wherein the microbial host cell is a Corynebacterium strain,
wherein said Corynebacterium strain is Corynebacterium glutamicum,
wherein said fermentable carbon substrate is selected from the group consisting of C-5 monosaccharides, C-6 monosaccharides, disaccharides, and tri-saccharides, and
wherein said Corynebacterium glutamicum has decreased expression of anthranilate phosphoribosyl transferase caused by reduced expression of trpD gene encoding anthranilate phosphoribosyl transferase, wherein said reduced expression is caused by a genetic modification of the trpD gene, and wherein said genetic modification is selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8 (claim 1);
claim 19 of the patent recites (in relevant part) wherein said fermentable carbon substrate comprises a C-5 monosaccharide comprising xylose; and
claim 20 of the patent recites (in relevant part) wherein said fermentable carbon substrate comprises a C-6 monosaccharide comprising glucose.
Given that the Corynebacterium glutamicum has decreased expression of anthranilate phosphoribosyl transferase yet maintains the ability to produce o-aminobenzoate, the Corynebacterium glutamicum of the claims of the patent is considered to have reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in instant claims 1 and 5.
The differences between the claims of the patent and the claims of this application are:
While the claims of the patent recite glucose and xylose as fermentable carbon sources for the production of o-aminobenzoate, the claims of the patent do not recite the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the patent do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the patent do not recite presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase as recited in claims 1 and 5;
While the claims of the patent recite xylose as a fermentable carbon source for the production of o-aminobenzoate, the claims of the patent do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the patent do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon substrate of the o-aminobenzoate production method of the claims of the patent to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the patent recite glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2) and 4), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by overexpressing an aroK gene and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the patent recite biological production of o-aminobenzoate by fermentation using a C. glutamicum and Jaeger teaches overexpressing an aroK gene and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 3), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the patent recite biological production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 5), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because the claims of the patent recite xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 6), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the patent modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the patent modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the patent modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 1, 5, 19, and 20 of the patent.
U.S. Patent No. 11,168,341 B2
Claims 1-3, 5, 10, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of U.S. Patent No. 11,168,341 B2 (cited on the attached Form PTO-892) in view of Jaeger and Yamada.
Claim 1 of the patent recites a process for preparing ortho-aminobenzoic acid or an ortho aminobenzoic acid derivative, comprising:
(I) fermenting a raw material with microorganisms, said raw material comprising at least one fermentable carbon-containing compound, wherein an ortho aminobenzoate- and/or an ortho aminobenzoic-acid-comprising fermentation broth is obtained and wherein the fermenting is carried out at a pH of ≥6.5 to prevent spontaneous precipitation of ortho aminobenzoic acid in the fermentation broth;
(II) optionally, pretreating the fermentation broth obtained in (I), said pretreatment comprising
(1) removing the microorganisms from the fermentation broth obtained in (I) without pH adjustment, wherein a microorganism-depleted fermentation broth is obtained, and/or
(2) decoloring the fermentation broth obtained in (I) or, when carrying out (II) (1), the microorganism-depleted fermentation broth obtained in (II) (1), without pH adjustment;
(III) treating the fermentation broth obtained in (I) or (II) (1) or (II) (2), in one-step with acid in a reactor to precipitate ortho aminobenzoic acid from the fermentation broth;
(IV) isolating the ortho aminobenzoic acid precipitated in (III), wherein mother liquor remains;
(V) optionally further purifying the ortho aminobenzoic acid from (IV);
(VI) optionally further converting the ortho aminobenzoic acid obtained in (IV) or (V) to form an ortho aminobenzoic acid derivative;
wherein (III) is carried out in the presence of seed crystals of ortho aminobenzoic acid for increasing the yield of ortho aminobenzoic acid, and the presence of the seed crystals of ortho aminobenzoic acid is achieved such that the fermentation broth and the acid are added to a suspension of the seed crystals that has been initially charged in the reactor, in which at least 90% of the seed crystals initially charged in the suspension, based on the total mass of all seed crystals initially charged in the suspension, are the polymorph form I of ortho aminobenzoic acid; and
claim 7 of the patent recites (in relevant part) the process as claimed in claim 1, in which the microorganisms in (I) comprise Corynebacterium glutamicum.
The differences between the claims of the patent and the claims of this application are:
The claims of the patent do not recite the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the patent do not recite reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the patent do not recite presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the patent do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon substrate of the o-aminobenzoate production method of the claims of the patent to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the patent recite glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2), 3), and 5), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the patent recite biological production of o-aminobenzoate by fermentation using a C. glutamicum and Jaeger teaches reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 4), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the patent recite biological production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 6), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because the claims of the patent recite xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 7), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the patent modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the patent modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the patent modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 1 and 7 of the patent.
U.S. Patent No. 11,453,897 B2
Claims 1-3, 5, 10, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 13, and 19 of U.S. Patent No. 11,453,897 B2 (cited on the attached Form PTO-892) in view of Jaeger and Yamada.
Claim 1 of the patent recites a process for preparing aminobenzoic acid or an aminobenzoic acid conversion product, comprising:
(I) fermenting a raw material comprising:
a fermentable carbon-containing compound, and
a nitrogen-containing compound,
in a fermentation reactor using a microorganism and a calcium salt, wherein the microorganism contains a genetic modification to accumulate aminobenzoic acid in the fermentation reactor,
so as to obtain a mixture suspended in an aqueous fermentation solution, the mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate;
(II) (1) isolating the
(1)(i) precipitated calcium aminobenzoate or
(1)(ii) mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate
obtained in step (I) from the aqueous fermentation solution,
(2) converting the aminobenzoate bound in the calcium aminobenzoate to a water-soluble form to form a water-insoluble calcium salt other than calcium aminobenzoate by adding an aqueous phase containing cations that form water-soluble aminobenzoate salts and anions that form water-insoluble calcium salts to the isolated calcium aminobenzoate from (1)(i) or to the mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate from (1)(ii),
so as to obtain a suspension comprising
(2)(i) the precipitated water-insoluble calcium salt or
(2)(ii) a mixture comprising undissolved microorganisms and the water-insoluble calcium salt
in an aqueous solution of aminobenzoate, and
(3) separating the aqueous solution of aminobenzoate obtained in step (2) from the precipitated water-insoluble calcium salt from (2)(i) or from the mixture comprising undissolved microorganisms and the water-insoluble calcium salt from (2)(ii);
(III) introducing carbon dioxide at a pressure of greater than or equal to 1.50 bar(abs.) into the aqueous solution of aminobenzoate separated off in step (II)(3) to separate aminobenzoic acid out, so as to form a suspension containing aminobenzoic acid in an aqueous solution;
(IV) isolating the aminobenzoic acid separated out in step (III) by lowering the pressure with release of carbon dioxide to give a carbon dioxide-depleted aqueous solution that has been freed of aminobenzoic acid separated out;
(V) using the aqueous solution obtained in step (IV) that has been depleted of carbon dioxide and freed of aminobenzoic acid separated out as a constituent of the aqueous phase added in step (II)(2); and
(VI) optionally further converting the aminobenzoic acid separated off in step (IV) to an aminobenzoic acid conversion product, wherein step (VI) comprises:
(1) decarboxylating the aminobenzoic acid to give aniline;
(2) decarboxylating the aminobenzoic acid to give aniline, followed by acid-catalyzed reaction of the aniline with formaldehyde to form di- and polyamines of the diphenylmethane series;
(3) decarboxylating the aminobenzoic acid to give aniline, followed by acid-catalyzed reaction of the aniline with formaldehyde to form di- and polyamines of the diphenylmethane series, followed by reaction with phosgene to form di- and polyisocyanates of the diphenylmethane series;
(4) decarboxylating the aminobenzoic acid to give aniline, followed by conversion of the aniline to an azo compound;
(5) converting the aminobenzoic acid to an amide; or
(6) converting the aminobenzoic acid to a conductive polymer, the conductive polymer optionally comprising polyanthranilic acid;
claim 13 of the patent recites (in relevant part) the process as claimed in claim 1, in which microorganisms of a type comprising Corynebacterium glutamicum is used in step (I); and
claim 19 of the patent recites the process of claim 1, wherein the genetic modification comprises a genetic modification to downregulate anthranilate phosphoribosyltransferase activity.
The differences between the claims of the patent and the claims of this application are:
The claims of the patent do not recite the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the patent do not recite reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the patent do not recite presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the patent do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon substrate of the o-aminobenzoate production method of the claims of the patent to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the patent recite glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2), 3), and 5), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the patent recite biological production of o-aminobenzoate by fermentation using a C. glutamicum and Jaeger teaches reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 4), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the patent recite biological production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 6), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because the claims of the patent recite xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 7), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the patent modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the patent modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the patent modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 1, 13, and 19 of the patent.
U.S. Patent No. 11,788,107 B2
Claims 1-3, 5, 10, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, and 13 of U.S. Patent No. 11,788,107 B2 (cited on the attached Form PTO-892) in view of Jaeger and Yamada.
Claim 1 of the patent recites a process for preparing aniline, comprising:
(I) providing a solution of aminobenzoic acid in aniline, wherein aniline is present in the solution in an amount of 20% to 85% by mass, based on the total mass of aminobenzoic acid and aniline; and
(II) converting aminobenzoic acid in the solution provided in step (I) to aniline in a reactor by thermal decarboxylation at a temperature of 165° C. to 500° C. without the presence of any catalyst extraneous to the system;
claim 12 of the patent recites the process as claimed in claim 1, in which the providing of the solution of aminobenzoic acid in aniline in step (I) comprises:
(I)(1) fermenting a raw material comprising at least
a fermentable carbon compound and
a nitrogen compound,
in a fermentation reactor using microorganisms to obtain an aminobenzoate- and/or aminobenzoic acid-containing fermentation broth,
(I)(2) obtaining aminobenzoic acid from the fermentation broth;
and
(I)(3) dissolving the aminobenzoic acid obtained from the fermentation broth in step (I)(1) in aniline; and
claim 13 of the patent recites (in relevant part) the process as claimed in claim 12, in which microorganisms used in step (I)(1) comprise Corynebacterium glutamicum.
The differences between the claims of the patent and the claims of this application are:
The claims of the patent do not recite the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the patent do not recite reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the patent do not recite presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase as recited in claims 1 and 5;
The claims of the patent do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the patent do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon substrate of the o-aminobenzoate production method of the claims of the patent to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the patent recite glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2), 3), and 5), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the patent recite biological production of o-aminobenzoate by fermentation using a C. glutamicum and Jaeger teaches reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 4), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the patent recite biological production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 6), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the patent by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because the claims of the patent recite xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 7), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the patent modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the patent modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the patent modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 1, 12, and 13 of the patent.
Co-pending Application No. 18/716,262
Claims 1-3, 5, 10, and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, and 14 of co-pending application no. 18/716,262 (reference application) in view of Jaeger and Yamada.
Claim 1 of the reference application recites a process for recovering aminobenzoic acid from an aqueous mother liquor containing dissolved aminobenzoic acid which is obtained in a crystallization of aminobenzoic acid, wherein the process comprises:
(A) fermenting a raw material containing a fermentable carbon-containing compound and a nitrogen-containing compound in the presence of microorganisms to form a fermentation process product containing aminobenzoate anions and/or aminobenzoic acid;
(B) (I) crystallizing aminobenzoic acid during the fermentation by establishing a pH in the fermentation in the range from 3.0 to 4.7, followed by removal of the aminobenzoic acid precipitated in the crystallization by filtration, sedimentation or centrifugation to obtain the aqueous mother liquor containing dissolved aminobenzoic acid,
(II) (1) partially crystallizing aminobenzoic acid during the fermentation, followed by removal of the aminobenzoic acid precipitated in the partial crystallization by filtration, sedimentation or centrifugation to obtain a solution, and (2) crystallizing aminobenzoic acid out of the solution by establishing a pH in the range from 3.0 to 4.7, followed by removal of the aminobenzoic acid precipitated in the crystallization by filtration, sedimentation or centrifugation to obtain the aqueous mother liquor containing dissolved aminobenzoic acid, or
(III) crystallizing aminobenzoic acid after the fermentation by establishing a pH in the fermentation process product in the range from 3.0 to 4.7, followed by removal of aminobenzoic acid precipitated in the crystallization by filtration, sedimentation or centrifugation to obtain the aqueous mother liquor containing dissolved aminobenzoic acid;
(C) extracting the aqueous mother liquor containing dissolved aminobenzoic acid with an alkanol having 8 to 12 carbon atoms to obtain a first alcoholic phase containing aminobenzoic acid and a first aqueous phase;
(D) re-extracting aminobenzoic acid from the first alcoholic phase with (I) an aqueous base solution or (II) an aqueous acid solution to obtain a second aqueous phase containing (I) anions of aminobenzoic acid or (II) cations of aminobenzoic acid and a second alcoholic phase; and
(E) crystallizing aminobenzoic acid out of the second aqueous phase (I) by guiding the second aqueous phase into the crystallization from (B)(I), (B)(II)(2) or (B)(III) that was conducted at a pH in the range from 3.0 to 4.7, and/or (II) by establishing a pH in the range from 3.0 to 4.7, in a step other than (B)(I), (B)(II)(2) and (B)(III), followed by the removal of the aminobenzoic acid thus precipitated by filtration, sedimentation or centrifugation;
claim 10 of the reference application recites (in relevant part) the process as claimed in claim 1, in which the microorganisms in step (A) comprise Corynebacterium glutamicum; and
claim 14 of the reference application recites (in relevant part) the process as claimed in claim 1, in which ortho-aminobenzoic acid is produced.
The differences between the claims of the reference application and the claims of this application are:
The claims of the reference application do not recite the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the reference application do not recite reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the reference application do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon-containing compound of the o-aminobenzoate production method of the claims of the reference application to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the reference application recite a fermentable carbon-containing compound for production of o-aminobenzoate by Corynebacterium glutamicum, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2), 3), and 5), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation using a C. glutamicum and Jaeger teaches reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 4), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 6), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because the claims of the reference application recite xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 7), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the reference application modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 1, 10, and 14 of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending Application No. 18/718,579
Claims 1-3, 5, 10, and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-7 of co-pending application no. 18/718,579 (reference application) in view of Jaeger and Yamada.
Claim 5 of the reference application recites (in relevant part) a process for producing oAB comprising microbial fermentation of a recombinant cell comprising a gene coding for a DAHP synthase as defined in SEQ ID NO. 11 or a variant thereof, with the proviso that in the variant of DAHP synthase the positions 76 and 211 remain unaltered;
claim 6 of the reference application recites the process as claimed in claim 5, wherein the microbial cell is a Corynebacterium sp.; and
claim 7 of the reference application recites the process as claimed in claim 5, wherein the recombinant cell additionally differs from the wild type of the relevant microorganism by the following features:
(i) reduced activity of anthranilate phosphoribosyltransferase compared to the respective wild type, but where residual activity must be present; and
(ii) deletion or inactivation of the gene coding for phosphoenolpyruvate carboxylase as defined in SEQ ID NO. 4.
The differences between the claims of the reference application and the claims of this application are:
The claims of the reference application do not recite the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the reference application do not recite reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the reference application do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon-containing compound of the o-aminobenzoate production method of the claims of the reference application to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the reference application recite a fermentable carbon-containing compound for production of o-aminobenzoate by Corynebacterium glutamicum, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2) and 3), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation using a C. glutamicum and Jaeger teaches reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 4), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 5), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because the claims of the reference application recite xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 6), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the reference application modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 5-7 of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending Application No. 18/871,845
Claims 1-3, 5, 10, and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 8 of co-pending application no. 18/871,845 (reference application) in view of Jaeger and Yamada.
Claim 1 of the reference application recites a process for obtaining an organic acid from an aqueous solution of the organic acid, wherein the organic acid comprises:
an aminobenzoic acid of the formula (I) in which R is CH3 or H, or
an aliphatic saturated dicarboxylic acid of the formula (II) in which n = 1 or 2,
said process comprising:
A) preparing the organic acid by a biological process or a chemical reaction, wherein
a) the organic acid is crystallized from an aqueous medium during or after the preparation, followed by
1) removing the fractions of the organic acid that have precipitated in the crystallization by a solid-liquid phase separation to leave a first aqueous solution of the organic acid, and
2) optionally depleting the fraction of the inorganic acid dissolved in the first aqueous solution of the organic acid by extracting organic acid with an organic extractant or by adsorbing organic acid on an adsorbent, followed by removing of-the organic extractant or adsorbent to obtain a second aqueous solution of the organic acid;
B) treating the first aqueous solution of the organic acid or the second aqueous solution of the organic acid with a metal salt, the metal ions of which include Mn²+, Fe²+ and/or Cu²+, to precipitate a metal compound of the organic acid, followed by removing the precipitated metal compound of the organic acid by a solid-liquid phase separation;
C) base treatment of the metal compound of the organic acid that has been removed with an aqueous base solution with precipitation of metal hydroxide and removal of precipitated metal hydroxide by a solid-liquid phase separation to leave a basic aqueous solution containing anions of the organic acid; and
D) crystallizing organic acid out of the basic aqueous solution containing anions of the organic acid that has been obtained in C) by addition of an inorganic acid;
claim 5 of the reference application recites the process as claimed in claim 1, in which the organic acid is the aminobenzoic acid of the formula (I); and
claim 8 of the reference application recites (in relevant part) the process as claimed in claim 5, in which A) comprises a biological process comprising the fermentation of a raw material containing a fermentable carbon-containing compound and a nitrogen-containing compound in the presence of microorganisms.
The differences between the claims of the reference application and the claims of this application are:
The claims of the reference application do not recite a cell of the Corynebacterium genus and the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the reference application do not recite reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the reference application do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon-containing compound of the o-aminobenzoate production method of the claims of the reference application to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the reference application recite fermentative production of o-aminobenzoate by a microorganism, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2), 3), and 5), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the microorganism of the o-aminobenzoate production method of the claims of the reference application by reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation using a microorganism and Jaeger teaches reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 4), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the microorganism of the o-aminobenzoate production method of the claims of the reference application by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 6), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the microorganism of the o-aminobenzoate production method of the claims of the reference application by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because Jager teaches xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 7), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the reference application modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 1, 5, and 8 of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending Application No. 19/587,856
Claims 1-3, 5, 10, and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 9 of co-pending application no. 19/587,856 (reference application) in view of Jaeger and Yamada.
Claim 1 of the reference application recites a process comprising the production of aminobenzoic acid, the process comprising:
(A) fermenting a fermentable carbon-containing compound and a nitrogen-containing compound in the presence of microorganisms to obtain a fermentation broth containing aminobenzoate anions and/or aminobenzoic acid;
(B) obtaining aminobenzoic acid from the fermentation broth;
(C) converting carbon dioxide to a reduction product comprising formic acid, ammonium formate, an alkali metal salt of formic acid, acetic acid, ammonium acetate or an alkali metal salt of acetic acid; and
(D) adding the reduction product from step (C) to the fermentation of step (A);
claim 3 of the reference application recites (in relevant part) the process as claimed in claim 1, in which ortho-aminobenzoic acid is produced; and
claim 9 of the reference application recites (in relevant part) the process as claimed in claim 1, in which the microorganisms in step (A) comprise Corynebacterium glutamicum.
The differences between the claims of the reference application and the claims of this application are:
The claims of the reference application do not recite the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the reference application do not recite reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the reference application do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon-containing compound of the o-aminobenzoate production method of the claims of the reference application to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the reference application recite a fermentable carbon-containing compound for production of o-aminobenzoate by Corynebacterium glutamicum, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2), 3), and 5), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation using a C. glutamicum and Jaeger teaches reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 4), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 6), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because the claims of the reference application recite xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 7), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the reference application modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 1, 3, and 9 of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending Application No. 19/588,540
Claims 1-3, 5, 10, and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of co-pending application no. 19/588,540 (reference application) in view of Jaeger and Yamada.
Claim 1 of the reference application recites (in relevant part) a process comprising the production of aminobenzoic acid, the process comprising
(A) providing a fermentation broth containing aminobenzoate anions, comprising: (A.1) fermenting a fermentable carbon-containing compound and a nitrogen-containing compound in the presence of Corynebacterium glutamicum microorganisms at a pH of greater than 5.5 and (A.2) removing the microorganisms;
(B) setting a pH of3.0 to 5.5 in the fermentation broth containing aminobenzoate anions by adding formic acid to precipitate aminobenzoic acid;
(C) removing aminobenzoic acid precipitated in step (B) to obtain a mother liquor containing formate anions and formic acid; and
(D) introducing 55.0% to 100% of the total mother liquor produced in step (C) into the fermentation according to step (A.1) while depleting the formate anions and formic acid by
(i) an added enzyme preparation, and/or
(ii) the microorganisms used in step (A) and/or
(iii) added additional microorganisms different from the microorganisms used in step (A); and
claim 7 of the reference application recites (in relevant part) the process as claimed in claim 1, in which ortho-aminobenzoic acid is produced.
The differences between the claims of the reference application and the claims of this application are:
The claims of the reference application do not recite the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the reference application do not recite reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the reference application do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon-containing compound of the o-aminobenzoate production method of the claims of the reference application to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the reference application recite a fermentable carbon-containing compound for production of o-aminobenzoate by Corynebacterium glutamicum, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2), 3), and 5), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation using a C. glutamicum and Jaeger teaches reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 4), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 6), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because the claims of the reference application recite xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 7), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the reference application modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 1 and 7 of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending Application No. 19/597,652
Claims 1-3, 5, 10, and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10, and 11 of co-pending application no. 19/597,652 (reference application) in view of Jaeger and Yamada.
Claim 1 of the reference application recites a process comprising the production of aminobenzoic acid, the process comprising:
(A) fermenting a raw material containing a reducing sugar and a nitrogen-containing compound in the presence of microorganisms in a fermentation reactor to form a fermentation product containing aminobenzoate anions, the pH being maintained in the range from 6.0 to 8.5 during the fermentation by adding an inorganic base,
(B) removing the microorganisms from the fermentation product to obtain a clarified fermentation product And
(C) precipitating aminobenzoic acid from the clarified fermentation product by setting a pH of 3.0 to 4.7 by adding a protic acid, and removing the precipitated aminobenzoic acid to leave behind a mother liquor, wherein the mother liquor obtained in step (C) is fed to step (A);
claim 8 of the reference application recites the process as claimed in claim 1, in which the reducing sugar is selected from glucose, fructose, xylose, arabinose, mannose, galactose, ribose, maltose, lactose or a mixture of any two or more thereof;
claim 10 of the reference application recites (in relevant part) the process as claimed in claim 1, in which the microorganisms are Corynebacterium glutamicum; and
claim 11 of the reference application recites (in relevant part) the process as claimed in claim 1, in which ortho-aminobenzoic acid is produced.
The differences between the claims of the reference application and the claims of this application are:
The claims of the reference application do not recite the percentages of glucose and xylose recited in claims 1, 2, 5, and 10;
The claims of the reference application do not recite reduced expression of anthranilate phosphoribosyltransferase compared to the wild type, but where there must be residual activity as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of shikimate kinase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase as recited in claims 1 and 5;
The claims of the reference application do not recite elevated activity of the xylose assimilation enzymes xylose isomerase and xylulokinase as recited in claims 1 and 5; and
The claims of the reference application do not recite carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose as recited in claims 3 and 11.
Regarding difference 1), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches fermentable carbon substrates including glucose and xylose (p. 20, lines 24-27).
Yamada teaches culturing Corynebacterium glutamicum in a culture medium comprising 45 g/L glucose and 45 g/L xylose for production of an L-amino acid (paragraphs [0290] and [0313]; Figure 7; p. 4, lines 46-50). Given a broadest reasonable interpretation, Yamada’s culture medium comprising 45 g/L glucose and 45 g/L xylose is encompassed by “a culture medium containing a mixture of glucose and xylose with a glucose content between 5% by weight and 86% by weight and a xylose content between 95% by weight and 14% by weight” in claims 1 and 5 and “the mixture of glucose and xylose has a glucose content between 16% by weight and 86% by weight, and xylose contributes the proportion lacking from 100% by weight” in claims 2 and 10.
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date for the fermentable carbon-containing compound of the o-aminobenzoate production method of the claims of the reference application to comprise 45 g/L glucose and 45 g/L xylose. One would have been motivated and would have expected success because the claims of the reference application recite a fermentable carbon-containing compound for production of o-aminobenzoate by Corynebacterium glutamicum, Jaeger teaches glucose and xylose as fermentable carbon substrates for production of o-aminobenzoate by Corynebacterium glutamicum, and Yamada teaches a culture medium comprising 45 g/L glucose and 45 g/L xylose that is suitable for culturing Corynebacterium glutamicum for production of an L-amino acid.
Regarding differences 2), 3), and 5), Jaeger teaches genetically engineered strains of Corynebacterium glutamicum as biocatalysts that are suitable for efficient fermentative production of o-aminobenzoate from fermentable carbon sources (p. 3, lines 17-18). Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the common aromatic pathway and L-tryptophan branch (p. 4, lines 20-23).
Regarding reduced expression of anthranilate phosphoribosyl-transferase, Jaeger teaches engineering of the trpD gene in C. glutamicum strains to reduce expression of a trpD gene by expressing a modified trpD gene in a C. glutamicum with a deleted trpD gene (p. 7, line 30 to p. 8, line 6; p. 38, line 26 to p. 40, line 6). Jaeger teaches the resulting strains produced enough L-tryptophan to enable biomass formation and accumulate significant amounts of o-aminobenzoate (p. 39, line 15 to p. 40, line 6). Jaeger teaches the trpD gene encodes anthranilate phosphoribosyl-transferase (p. 7, line 27 to p. 8, line 6).
Regarding elevated activity of shikimate kinase, Jaeger teaches engineering of the aroK and aroL genes in C. glutamicum strains by overexpressing aroK and aroL in order to prevent an accumulation of intermediates in the common aromatic amino acid biosynthesis pathway of C. glutamicum strains (p. 9, lines 21-30; p. 44, lines 16-32). Jaeger teaches aroK encodes shikimate kinase (p. 44, line 19). One of ordinary skill in the art would have recognized that overexpressing aroK would enhance the activity of shikimate kinase.
Regarding presence of a feedback-resistant 3-deoxyarabinoheptulosanate-7-phosphate synthase, Jaeger teaches engineering of the aroG gene in C. glutamicum strains by overexpressing a feedback-resistant aroG gene encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (p. 10, lines 7-11; p. 43, lines 3-24).
In view of the teachings of Jaeger, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as taught by Jaeger. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation using a C. glutamicum and Jaeger teaches reducing expression of trpD gene, overexpressing an aroK gene, and expressing a feedback-resistant aroG gene as genetic modifications for overproduction of o-aminobenzoate using a C. glutamicum.
Regarding difference 4), Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway (p. 3, lines 31-34; p. 54, line 6), teaches the metabolic pathway for production of o-aminobenzoate (i.e., anthranilate or anthranilic acid) and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase (Figures 1 and 3; p. 22, lines 24-29; p. 23, lines 4-5), teaches certain gene targets for metabolic engineering to generate an oAB producer are located in the aromatic biosynthesis pathway leading to o-aminobenzoate and subsequent to L-tryptophan (Figure 1) (p. 4, lines 19-20), and teaches the biosynthesis of L-tryptophan is strictly controlled at several steps in C. glutamicum and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan branch (p. 4, lines 20-23).
Yamada teaches enzymes of the L-tryptophan pathway include 3-phosphoshikimate 1-carboxyvinyltransferase (i.e., 5-enolpyruvylshikimate-3-phosphate synthase) and chorismate synthase (paragraphs [0094] and [0095]). Yamada teaches expression of genes encoding these enzymes is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan (paragraph [0095]).
In view of the combined teachings of Jaeger and Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by deleting the tyrR gene. One would have been motivated and would have expected success because the claims of the reference application recite production of o-aminobenzoate by fermentation, Jaeger teaches o-aminobenzoate is an intermediate of the L-tryptophan biosynthesis pathway, the metabolic pathway for production of o-aminobenzoate and L-tryptophan includes the enzymes 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase, and overproduction of o-aminobenzoate requires genetic removal of metabolic controls in the L-tryptophan pathway, and Yamada teaches expression of genes encoding 3-phosphoshikimate 1-carboxyvinyltransferase and chorismate synthase is controlled by the tyrosine repressor (tyrR), and the activities of these enzymes may be enhanced by deleting the tyrR gene in order to enhance production of L-tryptophan.
Regarding difference 6), Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum for production of an L-amino acid. The xylose assimilation pathway comprises xylose isomerase encoded by xylA gene and xylulokinase encoded by xylB gene (paragraph [0006]). Jaeger teaches imparting xylose assimilability by modifying a bacteria so that activity of proteins constituting a xylose assimilation pathway are increased (paragraph [0127]).
In view of the combined teachings of Yamada, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the Corynebacterium glutamicum of the o-aminobenzoate production method of the claims of the reference application by introducing a xylose assimilation pathway. One would have been motivated and would have expected success because the claims of the reference application recite xylose as a fermentable carbon substrate for production of o-aminobenzoate by Corynebacterium glutamicum and Yamada teaches introducing a xylose assimilation pathway to Corynebacterium glutamicum by increasing the activities of xylose isomerase and xylulokinase.
Regarding difference 7), the combination of Jaeger and Yamada does not teach or suggest carbon yield is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and it is the examiner’s position that the o-aminobenzoate production method of the claims of the reference application modified according to Jaeger and Yamada as described above would have inherently resulted in a carbon yield that is at least 0.138 mol of carbon in the form of o-aminobenzoate per mole of carbon consumed in glucose and xylose. Since the Office does not have the facilities for examining and comparing applicants’ method with the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada, the burden is on the applicant to show an unobvious difference between the claimed method and the o-aminobenzoate production method of the reference application modified according to Jaeger and Yamada. See MPEP 2112.IV and 2112.V.
Therefore, claims 1-3, 5, 10, and 11 of this application are unpatentable over claims 1, 8, 10, and 11 of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Status of the claims:
Claims 1-3, 5, 7, and 10-12 are pending.
Claims 7 and 12 are withdrawn from further consideration.
Claims 1-3, 5, 10, and 11 are rejected.
No claim is in condition for allowance.
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/David Steadman/Primary Examiner, Art Unit 1656
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