DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
The amended claim set filed on 30 July 2026 is acknowledged. Claims 14-27 are currently pending. Of those, claims 14-19, 21-22, and 24-27 are amended. There are no new claims and no claims are withdrawn. Claims 1-13 are cancelled. Claims 14-27 will be examined on the merits herein.
Response to Amendment
Applicants’ arguments filed 30 July 2026 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks” and the Non-Final Office Action mailed 30 April 2026 will be referred to as “NFOA”.
Objection(s) and Rejection(s) Withdrawn
The rejections of claims 14-15, 21-22, and 25-27 under 35 U.S.C. 112(b) are withdrawn in view of the amendments to the claims.
The objection to claims 16-19 and 23-24 as being dependent upon a rejected base claim is withdrawn in view of the new rejection(s) below.
New Rejection(s)
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 14-19 and 21-27 are newly rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 14 recites the limitations “a reaction to generate acetyl-CoA from pyruvic acid is enhanced as compared to a parent strain without genetic modification” and “a function of pyruvate kinase and/or phosphotransferase system is reduced as compared to the parent strain without genetic modification. These limitations are functional limitations, i.e., recites a feature “by what it does rather than by what it is”. The broadest reasonable interpretation of the claim is that the claim encompasses a genetically modified microorganism having an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid with any structural elements capable of enhancing a reaction to generate acetyl-CoA from pyruvic acid and reducing the function of a pyruvate kinase and/or phosphotransferase system as compared to the parent strain without genetic modification.
Claim 15 recites, “enhancement of a reaction catalyzed by pyruvate dehydrogenase complex and/or enhancement of a reaction catalyzed by pyruvate formate-lyase as compared to the parent strain without genetic modification.” The broadest reasonable interpretation of this functional limitation is that the claim encompasses a genetically modified microorganism having an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid with any structural elements capable of enhancing a reaction catalyzed by pyruvate dehydrogenase complex and/or enhancing a reaction catalyzed by pyruvate formate-lyase as compared to the parent strain without genetic modification.
Claim 16 recites, “enhancement of the reaction catalyzed by the pyruvate dehydrogenase complex is an enhancement by increased expression of the pyruvate dehydrogenase complex and/or increased activity of the pyruvate dehydrogenase complex as compared to the parent strain without genetic modification.” The broadest reasonable interpretation of this functional limitation is that the claim encompasses a genetically modified microorganism having an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid with any structural elements capable of increasing the expression of the pyruvate dehydrogenase complex and/or increasing the activity of the pyruvate dehydrogenase complex as compared to the parent strain without genetic modification.
Claim 17 recites, “increased expression of the pyruvate dehydrogenase complex is achieved by reducing the function of transcriptional repressor of the pyruvate dehydrogenase complex as compared to the parent strain without genetic modification.” The broadest reasonable interpretation of this functional limitation is that the claim encompasses a genetically modified microorganism having an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid with any structural elements capable of reducing the function of a transcriptional repressor of the pyruvate dehydrogenase complex as compared to the parent strain without genetic modification.
Claim 18 recites, “the increased activity of the pyruvate dehydrogenase complex is achieved by reducing the sensitivity of the pyruvate dehydrogenase complex to NADH as compared to the parent strain without genetic modification.” The broadest reasonable interpretation of this functional limitation is that the claim encompasses a genetically modified microorganism having an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid with any structural elements capable of reducing the sensitivity of the pyruvate dehydrogenase complex to NADH as compared to the parent strain without genetic modification.
Claim 19 recites, “the enhancement of the reaction catalyzed by pyruvate formate lyase is achieved by enhancement by the increased expression of pyruvate formate-lyase as compared to the parent strain without genetic modification.” The broadest reasonable interpretation of this functional limitation is that the claim encompasses a genetically modified microorganism having an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid with any structural elements capable of increasing the expression of pyruvate formate-lyase as compared to the parent strain without genetic modification.
Claim 21 recites, “the reaction that reduces 3-oxoadipyl-CoA to generate 3-hydroxyadipyl-CoA is further enhanced as compared to the parent strain without genetic modification.” The broadest reasonable interpretation of this functional limitation is that the claim encompasses a genetically modified microorganism having an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid with any structural elements capable of enhancing the reaction that reduced 3-oxoadipyl-CoA to generate 3-hydroxyadipyl-CoA as compared to the parent strain without genetic modification.
Claim 22 recites, “phosphoenolpyruvate carboxykinase reaction is further enhanced as compared to the parent strain without genetic modification.” The broadest reasonable interpretation of this functional limitation is that the claim encompasses a genetically modified microorganism having an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid with any structural elements capable of enhancing a phosphoenolpyruvate carboxykinase reaction as compared to the parent strain without genetic modification.
Claim 23 recites, “the microorganism does not undergo glucose metabolism via the phosphoketolase pathway.” The broadest reasonable interpretation of this functional limitation is that the claim encompasses a genetically modified microorganism having an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid with any structural elements that prevent the microorganism from undergoing glucose metabolism via the phosphoketolase pathway.
Claim 24 depends on claim 14 and does not further limit the structure of the genetically modified microorganism or the functional limitations.
Claim 25 recites, “a step of enhancing or reducing a function inherent in the microorganism by genetic modification, wherein the step comprises: step (a) of enhancing a reaction to generate acetyl-CoA from pyruvic acid as compared to the parent strain without genetic modification, and step (b) of reducing an enzyme function of pyruvate kinase and/or phosphotransferase system as compared to the parent strain without genetic modification.” The broadest reasonable interpretation of the claim is that the steps are achieved by any means of enhancing a reaction to generate acetyl-CoA from pyruvic acid and reducing an enzyme function of pyruvate kinase and/or phosphotransferase system as compared to the parent strain without genetic modification.
Claim 26 recites, “step (c) of enhancing the reaction that reduces 3-oxoadipyl-CoA to generate 3-hydroxyadipyl-CoA as compared to the parent strain without genetic modification.” The broadest reasonable interpretation of the claim is that the step is achieved by any means of enhancing a reaction that reduces 3-oxoadipyl-CoA to generate 3-hydroxyadipyl-CoA as compared to the parent strain without genetic modification.
Claim 27 recites, “step (d) of enhancing a phosphoenolpyruvate carboxykinase reaction as compared to the parent strain without genetic modification.” The broadest reasonable interpretation of the claim is that the step is achieved by any means of enhancing a phosphoenolpyruvate carboxykinase reaction as compared to the parent strain without genetic modification.
MPEP 2163.II.3.a.ii. states (emphasis added):
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above)….
A "representative number of species" means that the species which are adequately described are representative of the entire genus.
Claims 14-15, 21-22, and 25-27 each recite the enhancement of a reaction in the genetically modified microorganism. These limitations encompass a broad scope of elements that may result in the enhancement of a given reaction. Examples of enhancing a reaction known in the art before the effective filing date of the claimed invention include, but are not limited to, increasing the temperature of within the cell can increase the speed of chemical reactions, adding or modifying enzymes to catalyze a chemical reaction, increasing the concentration of a substrate (Alberts et al., pg. 1, para. 2, pg. 4-5, and pg. 5-6 and 7).
In contrast to the broad scope of structural elements taught in the art as capable of enhancing a reaction, the instant specification teaches only a limited number of structures of genetically modified microorganisms capable of doing so. With respect to claims 14 and 25, the instant specification teaches several ways of enhancing the reaction to generate acetyl-CoA from pyruvic acid; enhancing the reaction catalyzed by the pyruvate dehydrogenase complex (PDHc) by removing the transcriptional repressor PdhR (para. 26), increasing the expression of at least one or more enzymes that constitute PDHc (para. 29), reducing the sensitivity of PDHc to NADH (para. 30), and enhancing the reaction catalyzed by pyruvate formate-lyase (para. 31). With respect to claim 15, the ways of enhancing the reaction catalyzed by the PDHc taught in the specification are: removing the transcriptional repressor PdhR (para. 26), increasing the expression of at least one or more enzymes that constitute PDHc (para. 29), and reducing the sensitivity of PDHc to NADH (para. 30). With respect to claim 15, the ways of enhancing the reaction catalyzed by pyruvate formate-lyase are: enhancing the catalytic activity of pyruvate formate-lyase or increasing the expression of pyruvate formate-lyase (para. 33). With respect to claims 21 and 26, the way of enhancing the reaction that reduced 3-oxoadipyl-CoA to generate 3-hydroxydipyl-CoA described in the specification is enhancing the activity of the enzyme that catalyzes the reaction (3-oxoadipyl-CoA reductase) by introducing the enzyme gene from outside the microorganism, increasing the copy number of the gene, and modifying the promoter region or the ribosome binding site upstream of the coding region of the gene (para. 49). With respect to claims 22 and 27, the ways of enhancing the phosphoenolpyruvate carboxykinase reaction are enhancing the activity of the enzyme that catalyzes the reaction by introducing the enzyme gene from outside the microorganism, increasing the copy number of the gene, and modifying the promoter region or the ribosome binding site upstream of the coding region of the gene (para. 44). As is shown by the teachings of the art, the instant specification’s teachings regarding the enhancement of reactions is narrow in comparison to the full scope claimed, and thus, the teachings of the specification are not representative of the full scope of structural features capable of achieving the functions recited in claims 14-15, 21-22, and 25-27.
Claims 14, 23, and 25 each recite the reduction of enzyme function or activity or elimination of a metabolic pathway in the genetically modified microorganism. Examples of reducing enzyme function known in the art before the effective filing date of the claimed invention include, but are not limited to, changing the pH or temperature of the cell, utilizing an inhibitor to prevent the enzyme from binding its substrate (Robinson, pg. 16-19), reducing the expression of the gene encoding the enzyme by deleting one or more copies of the gene, or preventing transcription and/or translation of the gene encoding the enzyme. Similarly, eliminating a metabolic pathway in an organism may be achieved, for example, through deletion of one or more genes encoding proteins in said pathway, eliminating transcription and/or translation of genes encoding proteins in said pathway, or by preventing the proteins of the pathway from utilizing particular substrates (e.g., cultivating the organism in a media that does not contain a particular substrate) (Alberts et al., pg. 5-6 and 7). As is shown by the teachings of the art, the instant specification’s teachings regarding the reduction of enzyme function or activity is narrow in comparison to the full scope claimed, and thus, the teachings of the specification are not representative of the full scope of structural features capable of achieving the functions recited in claims 14, 23, and 25.
In contrast to the broad scope of structural changes that could result in the reduction of enzyme function or elimination of a metabolic pathway, the instant specification only teaches some structures capable of achieving the claimed functions. With respect to claims 14 and 25, ways of reducing the function of pyruvate kinase and/or phosphotransferase system are: reducing the activity of the enzymes by downregulating the genes encoding the enzymes through gene mutation treatment such as by gene mutation agent or ultraviolet irradiation, deleting a portion or the whole of the nucleotide sequence, or introduction of a stop codon (para. 35). With respect to claim 23, the instant specification teaches that the genetically modified microorganism may be a host organism that does not undergo the phosphoketolase pathway or has a deletion of the phosphoketolase gene (para. 51).
Claims 16-19 each recite the increased expression or activity of an enzyme in the genetically modified cell. Examples of ways to enhance the expression or activity of an enzyme known in the art before the effective filing date of the claimed invention include, but are not limited to utilizing promoters to increase transcription, utilizing chaperones to assist protein folding, codon optimization, and improving the culturing system of microorganisms (Liu et al., pg. 213, left col., pg. 214, right col., and pg. 215, left col.).
In contrast to the broad scope of structures capable of increasing expression or activity of an enzyme, the instant specification only teaches a limited number of mays to achieve the claimed functions. With respect to claim 16, the ways of increasing the expression of PDHc taught by the specification are: introducing one or more PDHc genes from outside the microorganisms, increasing the copy numbers of the gene cluster, modifying the promoter regions or the ribosome binding site upstream of the coding regions of the cluster (para. 29), and reducing the sensitivity of PDHc to NADH (para. 30). With respect to claim 17, the instant specification teaches that the activity of PDHc is enhanced in the absence of pdhR and teaches the deletion of pdhR (para. 92 and 116-117). With respect to claim 18, the way of reducing the sensitivity of PDHc to NADH taught in the specification are substituting or adding a gene for a E354K and/or H322Y Lpd variant from E. coli or using Lpd from K. pneumoniae (para. 30). With respect to claim 19, the ways of increasing the expression of pyruvate formate-lyase taught by the instant specification are: introducing the pyruvate formate-lyase gene from outside the microorganism, increasing the copy number of the gene, and modifying the promoter region or the ribosome binding site upstream of the coding region of the gene (para. 33). As is shown by the art, the teachings of the specification are not representative of the full scope of structural elements capable of achieving the functions recited in claims 16-19.
Therefore, claims 14-19 and 21-27 are rejected because the specification fails to sufficiently describe a representative number of species of genetically modified microorganism.
Allowable Subject Matter
Claim 20 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY M MORGAN whose telephone number is (703)756-5388. The examiner can normally be reached M-F 9-5 ET.
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/BAILEY M MORGAN/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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