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 .
Status of the Application
1. Claims 1-12 are pending and subject to examination on the merits. Claims 9-12 are withdrawn from consideration as being drawn to non-elected subject matter. Claims 1-8 are currently under examination.
Election/Restrictions
2. Claims 9-12 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10 August 2026.
Priority
3. Acknowledgment is made for the Applicant’s claim for domestic priority based on the US provisional application PRO 63/596,559 filed 06 November 2023.
Claim Rejections - 35 USC § 112(a)
4. 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:
5. Claims 1-6 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 recombinant asparagine racemase converting L-asparagine to D-asparagine derived from an aspartic or glutamic acid racemase from E. coli, wherein the asparagine racemase comprises the mutation(s) Q52E or Q52E and E199D/E199H and retains the active site amino acids S11, T83, N84, T85, C197, T198, and E199.
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.
6. The claims are drawn to a recombinant asparagine racemase converting L-asparagine to D-asparagine derived from an aspartic or glutamic acid racemase from E. coli, wherein the asparagine racemase comprises the mutation(s) Q52E or Q52E and E199D/E199H and retains the active site amino acids S11, T83, N84, T85, C197, T198, and E199. The specification does not describe all the enzymes that can convert L-asparagine to D-asparagine. Additionally, there is no reference sequence in claims 4-6 to mutate or retain the listed amino acids, where the specification has two SEQ ID NOs listed. Here the specification is incomplete and it mandates that those skilled in the art must then figure out how to create the aimed invention. Thus, the claims do not find adequate support in any place in the specification to show that possession of any enzyme that can covert L-asparagine to D-asparagine with a retained active site and mutations of an unknown starting sequence. 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)
7. 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.
8. Claims 4-6 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.
The claims are deemed indefinite as they are drawn to amino acid numbering of 52, 11, 83, 84, 85, 197, 198, and 199; however, the claims do make clear what amino acids these numbers correspond to. Specifically, there is no reference sequence listed in the claim to which these amino acids will be conserved or mutated. It is suggested to insert a sequence number such as SEQ ID NO: 2 to which the amino acids correspond to (e.g. are not limited to but correspond to).
Claim Rejections - 35 USC § 101
9. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
10. Claims 1 and 8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a natural phenomenon) without additional elements that integrate the judicial exception into a practical application. An analysis with respect to the claims as a whole reveals that they do not include additional elements that integrate the judicial exception into a practical application. See MPEP 2106.
Analysis of subject-matter eligibility under 35 U.S.C. § 101 requires consideration of the following steps:
Step (1) whether the claim is directed to one of the four categories recited in §101 (process, machine, manufacture or composition of matter);
Step (Revised 2A - Prong 1) do the claims recite an abstract idea (mathematical concepts, mental processes or method of organizing human activity), law of nature or natural phenomenon;
Step (Revised 2A - Prong 2) do the claims recite additional elements that integrate the judicial exception into a practical application; and
Step (2B) whether the claim as a whole recites something that amounts to significantly more than the judicial exception. (See 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG)).
Step 1: Yes; the claims are directed to a composition of matter.
Step 2A – Prong 1: Yes, the claims recite a natural phenomenon, namely, a racemase that converts L-asparagine to D-asparagine.
Step 2A – Prong 2: No, the claims do not recite any additional elements that integrate the judicial exception into a practical application because the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed with the racemase that converts L-asparagine to D-asparagine. See Espaillat et al (Espaillat et al., 2013, Biological Crystallography—cited herein), who teach a broad spectrum amino-acid racemase, specifically BsrV of Vibrio cholerae, that converts L-asparagine to D-asparagine (abstract and Fig. 1D).
Step 2B: As noted in answering that of 2A – This judicial exception is not integrated into a practical application because enzymes that convert L-asparagine to D-asparagine are naturally occurring. The utilization of the limitation “recombinant” does not distinguish the claimed protein from one that exists in the natural world, since it only refers to how it was created. As such, there is no distinguishable modification to delineate this enzyme from any other naturally occurring enzyme.
Claim Rejections - 35 USC § 102
11. 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.
12. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
13. Claims 1-2 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Espaillat et al (Espaillat et al., 2013, Biological Crystallography—cited herein). Regarding claims 1-2 and 8, drawn to an asparagine racemase or pharmaceutical composition thereof that converts L-asparagine to D-asparagine, Espaillat et al. teaches a broad spectrum amino-acid racemase, specifically BsrV of Vibrio cholerae, that converts L-asparagine to D-asparagine (abstract and Fig. 1D).
Claim Rejections - 35 USC § 103
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 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Ahn et al (Ahn et al., 2015, FEBS Lett—cited herein). Regarding claims 1-3 and 8, drawn to a recombinant asparagine racemase or pharmaceutical composition thereof (claim 8) capable of converting L-asparagine to D-asparagine (claim 1), wherein said racemase is unidirectional (claim 2), and wherein the racemase is derived from an aspartic or glutamic acid racemase of E. coli (claim 3), Ahn et al. teaches a L-aspartate/glutamate specific racemase from E. coli, where said racemase catalyzes the conversion of L-amino acids to D-amino acids, that can be used as precursors for pharmaceuticals (Introduction, 1st paragraph), and wherein said protein was isolated and concentrated in a buffer of Tris-HCl and beta-mercaptoethanol (2.1 protein preparation). Regarding claims 4-7, drawn to an asparagine racemase comprising SEQ ID NO: 2 (claim 7), wherein said racemase has a mutation of Q52E (claim 4), wherein said protein retains the active site amino acids: S11, T83, N84, T85, C197, T198, and E199 (claim 5) or (S11, T83, N84, T85, C197, T198, and a mutation of E199 to E199D or E199H (claim 6), Ahn et al. teaches Ecl-DER with a sequence that is 99.7% identical to SEQ ID NO: 2 of the instant claims (See Supplemental File: 20260820_122310_us-18-936-118-2.rup, entry 1, duplicate 6).
Ahn et al. does not teach the point mutations of Q52E or E199D, but Ahn et al. does teach that these specific amino acids are involved in glutamate binding (Fig. 1). However, the claims would still be obviated because the Q52E and E199D mutations are conservative changes, and the MPEP (MPEP 2144.08(II)(A)(4)(c) further states that:
In the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution ("the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein." Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (W. H. Freeman & Co., 2d ed. 1990).
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 to introduce conservative mutations at the identified glutamate binding sites of the aspartate/glutamate racemase of Ahn et al. to determine specific substrate specifics, as taught by Ahn et al. One would be motivated to alter these amino acids to produce D-amino acids, which are industrially relevant in pharmaceuticals, as taught by Ahn. There would be reasonable expectation of success, yielding no surprising results when utilizing the teachings of Ahn et al. to introduce conservative mutations in the aspartate/glutamate racemase at the glutamate binding sites to create an asparagine racemase, since conservative mutations are obvious.
Conclusion
16. 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
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