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 .
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 29 January 2026 has been entered.
Status of the Application
2. Claims 52-58 and 72 are pending and subject to examination on the merits. Claims 52-58 and 72 are currently under examination.
Priority
3. Acknowledgment is made for the Applicant’s claim for domestic priority based on the US provisional application PRO 62/860,160 filed 11 June 2019.
Withdrawn Rejections/Objections
4. The 35 U.S.C. 112(b) indefiniteness rejection of claim 55 for the recitation of “Table 5 and combinations thereof” is withdrawn, since the claim was amended to list the amino acid positions instead of referencing the table.
5. The 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) anticipation rejection to claims 52-38 and 72 over Burk et al is withdrawn, since the claims were amended to recite “non-naturally occurring.”
Claim Rejections - 35 USC § 112(a)
6. 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.
Written Description:
7. Claims 52-58 and 72 are 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.
The claims are drawn to a non-naturally occurring engineered TA enzyme comprising at least one alteration of an amino acid of SEQ ID NO: 1, wherein said enzyme is capable of forming adipate semialdehyde substrate, forming adipate semialdehyde substrate at a greater rate than the wildtype, and/or having greater affinity for an adipate semialdehyde substrate compared to a wildtype, and wherein said enzyme is expressed in a cell co-expressing a 3-oxoadipyl-CoA thiolase, a 3-oxoadipyl-CoA dehydrogenase, and a 3-oxoadipyl-CoA dehydratase, producing at least 10% more 6ACA than a control cell expressing the wildtype TA.
MPEP 2163(1):
35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en bane); Vas-Gath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111, 1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim's enablement is not equally conclusive of that claim's satisfactory written description"). The written description requirement has several policy objectives. "[T]he 'essential goal' of the description of the invention requirement is to clearly convey the information that an applicant [inventor] has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). "The 'written description' requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor's obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee [inventor] was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent's term.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Gath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
8. The claims are drawn to a non-naturally occurring engineered TA enzyme comprising at least one alteration of an amino acid of SEQ ID NO: 1, wherein said enzyme is capable of forming adipate semialdehyde substrate, forming adipate semialdehyde substrate at a greater rate than the wildtype, and/or having greater affinity for an adipate semialdehyde substrate compared to a wildtype, and wherein said enzyme is expressed in a cell co-expressing a 3-oxoadipyl-CoA thiolase, a 3-oxoadipyl-CoA dehydrogenase, and a 3-oxoadipyl-CoA dehydratase, producing at least 10% more 6ACA than a control cell expressing the wildtype TA. The variability of engineered TA enzymes claimed is enormous, since the claim language encompasses any single or combinatorial change to any amino acid position in the polypeptide, i.e. any position substituted by any amino acid and any combinations thereof. The variability of selecting single mutations and/or combinatorial mutational subsets is enormous, since the current claim language recites a restriction-less substitution change at any and all positions with any amino acid.
The specification does not describe any and every possible change that could be made in respects to the polypeptide involving the “comprising” language. At most the specification describes the 233 possible mutants recited in Table 5 (p. 50-60). How an amino acid substation at a single position, and specifically with which amino acid the position is substituted with, i.e. conservative or non-conservative, is difficult to predict across every position of the polypeptide and even more difficult across multiple positions in the polypeptide. Here the specification is incomplete and it mandates that those skilled in the art must then figure out how to determine the aimed invention. Thus, the claims do not find adequate support in any place in the specification to show that possession of a non-naturally occuring engineered transaminase comprising one or more substitutions at SEQ ID NO: 1. The courts have established:
Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336 (Fed. Cir. 2013):
A patent, however, "is not a reward for the search, but compensation for its successful conclusion." Ariad, 598 F.3d at 1353 (quoting University of Rochester, 358 F.3d at 930 n.10). For that reason, the written description requirement prohibits a patentee from "leaving it to the ... industry to complete an ufinished invention.” Id.
Claim Rejections - 35 USC § 112(b)
9. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
10. Claims 54 and 72 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
11. The terms “T149” in line 5 and “A388” in line 8 of claim 54 render the claim indefinite (these positions are also referenced as G149 and C388, which are the correct amino acids recited in SEQ ID NO: 1). The terms “T149” and “A388” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Positions 149 and 388 in SEQ ID NO: 1 are not T149 or A388. The positions listed in the sequence listing are G149 and C388 in SEQ ID NO: 1. The positions set forth in the sequence listing is how the claim will be interpreted for examination purposes: specifically, an amino acid change at G149 and an amino acid change at C388 in SEQ ID NO: 1. Claim 72 is also included in the instant rejection, since it does not mitigate the issues.
12. The terms “N70” in line 18 and “V186” in line 45 of claim 72 render the claim indefinite (these positions are also referenced as D70 and L186, which are the correct amino acids recited in SEQ ID NO: 1). The terms “N70” and “V186” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Positions 70 and 186 in SEQ ID NO: 1 are not N70 or V186. The positions listed in the sequence deposit are D70 and L186 in SEQ ID NO: 1. The positions set forth in the sequence listing is how the claim will be interpreted for examination purposes: specifically, an amino acid change at D70 and an amino acid change at L186 in SEQ ID NO 1.
Claim Rejections - 35 USC § 103
13. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
14. 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.
15. Claims 52-56 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Burk et al (Burk et al., 2010, WO 2010/129936 A1—cited previously) and Guo and Berglund (Guo and Berglund, 2017, Green Chem—cited herein). Regarding claim 52, drawn to an engineered transaminase enzyme comprising at least one alteration of an amino acid of SEQ ID NO: 1 or 13 or 31, Burk et al. teaches the gene product of gabT of Pseudomonas fluorescens as a transaminase that can be utilized in the caprolactam pathway (p.143, table below line 11; Figure 8), where GabT is 57.4% homologous to SEQ ID NO: 1 (See attached sequence alignment: “gabT Pseudo vs. SEQ ID NO: 1,” downloaded 25 March 2026 from <https://abss.uspto.gov/abss4examiners/> and provided herein as a PDF). In regards to claim 53, drawn to the engineered transaminase being capable of forming 6-aminocaproic acid from adipate semialdehyde substrate, Burk et al. teaches the production of caprolactam and/or 6-aminocaproic acid using adipyl-COA as a precursor as shown in Figure 8, utilizing enzymes, such as gabT gene product, and further, the transaminase is capable of converting adipate semialdehyde to 6-aminocaproic acid (p. 141-142, Example VIII: production of Caprolactam and 6-Aminocaproic Acid via Adipyl-CoA; p. 143, table below line 11; Figure 8). Regarding claims 54-56 and 72, drawn to the engineered transaminase comprising at least two or more amino acid alterations selected from a number of positions, specifically V114, S136, T148, P153, I203, I204, P206, V207, V111, T216, A237, T264, M265, L386,G19, C22, D70, R94, D99, T109, El12, Al13, F137, G144, G149, K150, Y154, S178, L186, Q208, L234, T242, A315, K318, R338, G336, L386, V390, A406, S416, A421, G17, M21, A50, A76, Y77, Q78, I79, G84, F107, T108, K119, G139, M142, A152, P153, E205, G209, G211, D238, M285, A290, G291, G292, L293, Y297, M353, S387, C388, and G392 or a combination thereof of SEQ ID NO: 1, Burk et al. teaches the gabT gene product comprising specific mutations: S136A, V111S, T216A, D70N, R94A, G144T, L186I, A315E, K318H, R338Q, G336A, V390T, S416E, G84P, M142Y, and A290P, where S136A, T216A, D70N, L186I, and M142Y are named in claims 55 and 72 (See attached sequence alignment: “gabT Pseudo vs. SEQ ID NO: 1,” downloaded 25 March 2026 from <https://abss.uspto.gov/abss4examiners/> and provided herein as a PDF).
Burk et al. does not teach a non-naturally occurring engineered TA.
Guo and Berglund teach the optimization of transaminases to optimize their performance (p. 333, abstract, lines 4-5). Guo and Berglund teach the identification of candidate transaminases to optimize via enrichment cultivation, metabolic function analysis, GC-based, homologous sequence searching, motif-based sequence searching, sequences of known functions, protein structure databases (Table 1), and the subsequent optimization of various identified transaminases by protein engineering (typically random mutagenesis) (Table 2). Specifically, there are multiple Pseudomonas spp. on the both tables, and a transaminase in P. fluorescens that has been identified as a candidate transaminase (Table 1).
Therefore, it 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 combine the teachings of Burk et al. with Guo and Berglund to engineer a non-naturally occurring transaminase with some alteration to SEQ ID NO: 1 of the instant claims to prepare chiral amino compounds. As taught by Guo and Berglund (abstract, lines 1-2). One would be motivated to combine these teachings to arrive at the instant claims to optimize a transaminase for use in the industrial production of high-value chemical products, as taught by Guo and Berglund (abstract, lines 9-10). Further, one would be motivated to optimize a transaminase to utilize said transaminase in a more efficient and more economical manner, as taught by Guo and Berglund (abstract, lines 4-5). There would be a reasonable expectation of success, yielding no surprising results when combining the teachings of Burk et al. with Guo and Berglund to manufacture a transaminase with at least one substitution in reference to SEQ ID NO: 1, since Guo and Berglund teach multiple species and instances of engineering transaminases for use in industrial manufacturing.
16. Claims 57-58 are rejected under 35 U.S.C. 103 as being obvious over Burk et al (Burk et al., 2010, WO 2010/129936 A1—cited previously) and Guo and Berglund (Guo and Berglund, 2017, Green Chem—cited herein) as applied to claims 52-56 and 72 above.
The teachings of Burk et al. and Guo and Berglund are discussed above and incorporated into the instant rejection.
Burk et al. and Guo and Berglund do not expressly teach the engineered transaminase having the physicochemical properties of: (1) has at least 20% higher than the activity of the wild type TAs of SEQ ID NOs: 1, 13, or 31 and (2) is able to produce 10% more 6ACA than a control cell with wild type TA as recited in claims 57 and 58. However, according to MPEP 2112, the inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 103. The gabT gene product recited in Burk et al. has at least one amino acid alteration of SEQ ID NO: 1 as the engineered transaminase recited in claim 52, 57, and 58, and furthermore, an engineered transaminase of Burk et al. and Guo and Berglund is able to produce 6ACA in an identical pathway. As such, it is the examiner’s position that an engineered transaminase of Burk et al. and Guo and Berglund comprises the characteristics of: (1) has at least 20% higher than the activity of the wild type TAs of SEQ ID NOs: 1, 13, or 31 and (2) is able to produce 10% more 6ACA than a control cell with wild type TA as recited in claims 57-58. Since the Office does not have the facilities for examining and comparing applicant’s enzyme with the enzyme of the prior art, the burden is on the applicant to show a novel or unobvious difference between the recited product and the recited product of the prior art (i.e., that the enzyme of the prior art does not possess the same physicochemical characteristics of the recited enzyme). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Applicant’s Arguments and Examiner’s Rebuttal:
The applicant traverses the previous 35 U.S.C. 102(a)(1) and 102(a)(2) anticipation rejection of record of claims 52-58 and 72 over Burk et al. due to amending the claims to recite “non-naturally occurring” in the claim pre-amble.
The examiner agrees insofar that the original rejection of record did not consider this claim limitation; however, this limitation has been addressed in the new rejection of record found above, where specifically the rejection of record above provides motivation for the utilization of one of the naturally occurring transaminases recited in Burk et al (gabT) and engineering/optimizing said transaminase to enhance its use in the industrial production of high-value chemical products and/or the utilization of the transaminases in a more efficient and more economical manner.
The examiner does not find the arguments presented by the Applicant persuasive, and for these reasons, the rejections of record above apply.
Conclusion
17. All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
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/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656