DETAILED ACTION
Status of the Application
Claims 1-2, 5, 8, 12-15, 31-37, 43-44, 47 are pending.
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 amendment of claims 1-2, 5, 12-14, 32, 43-44, addition of claim 47, and cancellation of claims 20-22 as submitted in a communication filed on 3/26/2026 is acknowledged.
Applicant elected with traverse Group 1, claims 2, 5, 8, 12-17, 18, 31-33, 41-42, drawn in part to a composition that comprises nanostructures that comprise an esterase, wherein the esterase comprises SEQ ID NO: 1, and further elected without traverse the combination of end-capping modified aromatic dipeptides and non-modified aromatic dipeptides, and manganese, in a communication filed on 12/12/2025.
As previously indicated, claim 1 is no longer a generic linking claim. New claim 47 is directed to the elected invention. Claims 34-37, 43-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/12/2025.
Claims 1-2, 5, 8, 12-15, 31-33, 47 are at issue and will be examined to the extent they encompass the elected invention.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/20/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 1 is objected to due to the recitation of “…or a combination thereof; said esterase is a phosphotriesterase like lactonase…..”. To enhance clarity and to be consistent with commonly used claim language, the term should be amended to recite “…or a combination thereof; wherein said esterase is a phosphotriesterase like lactonase…..”. Appropriate correction is required.
Claim 1 is objected to due to the recitation of “said PPL is the wild-type putative parathion hydrolase (PPH) from M. tuberculosis having a sequence comprising the amino acid sequence of SEQ ID NO: 1”. To enhance clarity and simplify the language, the claim should be amended to recite “said PPL is the wild-type putative parathion hydrolase (PPH) from M. tuberculosis having a sequence that comprises SEQ ID NO: 1”. Appropriate correction is required.
Claim 47 is objected to due to the recitation of “..hydrolase…has a sequence consisting of the amino acid sequence of SEQ ID NO: 1”. To enhance clarity and simplify the language, the claim should be amended to recite “..hydrolase…has a sequence consisting of SEQ ID NO: 1”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
Claims 1-2, 5, 8, 12-15, 31-33 were 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 pre-AIA the applicant regards as the invention. In view of Applicant’s amendments, the previous grounds of rejection are hereby withdrawn.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
Claims 1-2, 5, 8, 12-15, 31-33 were 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 and enablement requirements. In view of Applicant’s amendments, which limit the genus of lactonases to lactonases that comprise/consist of SEQ ID NO: 1, these rejections are hereby withdrawn.
Claim Rejections - 35 USC § 103 (AIA )
Claims 1-2, 5, 8, 12-15, 31-33 remain rejected and new claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over Marcu et al. (U.S. Publication No. 2016/0326215 published 11/10/2016; cited in the IDS) in view of Afriat et al. (Biochemistry 45(46):13677-13686, 11/21/2006; cited in the IDS; hereinafter Afriat 1), Park et al. (Enzyme and Microbial Technology 51:81-85, 2012; cited in the IDS), Chen et al. (Int. J. Mol. Sci. 14:17477-17500, 2013), and Afriat et al. (GenBank accession No. ACF57854 published 7/27/2008; cited in the IDS; hereinafter Afriat 2).
This rejection has been discussed at length in the prior Office action. It is maintained and further applied to new claim 47 for the reasons of record and those set forth below.
Applicant states that PPH is a complex metalloenzyme that requires Mn2+ and that one of skill in the art would have no reasonable expectation of success that PPH would maintain both its activity and stability inside a self-assembled peptide environment compared to the robust HRP enzyme used by Park et al. Applicant also states that the specification discloses a dramatic and unexpected increase in shelf life as well as a significant disease inhibition in field trials, citing Figures 5B and 6B. Applicant states that neither Marcu et al. nor Park et al. could have predicted the superior results found. Applicant states that while general encapsulation is known, the specific compatibility of the Boc-FF/FF peptides with a Mn2+-dependent lactonase is not a predictable result of routine engineering.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection or avoid the rejection of new claim 47. The Examiner acknowledges the results disclosed in the specification as well as the requirement of Mn2+ for the protein of SEQ ID NO: 1. However, the Examiner disagrees with Applicant’s contention that the claimed invention is not obvious over the teachings of the cited prior art.
Claims 1-2, 5, 8, 12-15, 31-33, 47 are directed in part to a composition comprising a plurality of nanospheres, microspheres, and/or tubular nanostructures, wherein said nanospheres, microspheres, and tubular nanostructures comprise the PLL of SEQ ID NO: 1 wherein said PLL comprises a tag, wherein said composition has a pH of 7-11 and comprises a Tris buffer as well as Mn divalent ions, wherein the nanospheres, microspheres, or tubular nanostructures are made from aromatic dipeptides, including phenylalanine-phenylalanine dipeptides, wherein the aromatic dipeptides are a combination of non-modified aromatic dipeptides and end-capping aromatic dipeptides, wherein the end-capping aromatic dipeptides are protected at the N- and/or C-terminus, wherein the end-capping modified aromatic dipeptides are protected with Boc or Fmoc, wherein the molar ratio of end-capping aromatic dipeptides to non-modified aromatic dipeptides is between 1:1 to 1:100, wherein the diameter of the nanostructures is between 50 nm to 2 µm, or the length of the nanostructures is between 10 nm to 2000 nm (2 µm), and wherein the composition can be in dried form.
With regard to the argument that one of skill in the art would have no reasonable expectation of success that PPH would maintain both its activity and stability inside a self-assembled peptide environment compared to the robust HRP enzyme used by Park et al., it is noted that there is no evidence in the specification or the prior art indicating that an enzyme that requires Mn2+ and is provided with a buffer that comprises Mg divalent ions would not maintain its activity and stability. It is noted that at the time of the invention, it was well known in the art, as evidenced by Afriat 1 and Afriat 2, that the M. tuberculosis of Afriat 1, which consists of SEQ ID NO: 1, has lactonase activity and that the highest enzymatic activity was observed in the presence of Mn2+. One of skill in the art would have reasonably expected that if the protein of SEQ ID NO: 1 is in a buffer such that the one taught by Afriat 1, which comprises Mn2+, the protein of SEQ ID NO: 1 would be enzymatically active. If the argument is that encapsulation of enzymes that require Mn2+ could lead to inactivation of the enzymes, it is noted that there is no indication in the prior art or the specification teaching or suggesting that as a result of encapsulation, enzymatic inactivation is more likely to occur with enzymes that require Mn2+ even when the enzyme is encapsulated in a buffer containing Mn2+ . On the contrary, Park et al. teach that enzyme stabilization is frequently achieved by immobilization, entrapment or encapsulation and that recently dipeptide (phenylalanine-phenylalanine) nanostructures have been recognized as a potential encapsulation approach (page 81, Introduction). Therefore, while it is agreed that at the time of the invention, there was no absolute certainty that as a result of encapsulation, the protein of SEQ ID NO: 1 would still be enzymatically active, the teachings of Park et al. regarding the successful encapsulation of other enzymes known in the prior art, as well as the encapsulation disclosed by Park et al. would have given one of skill in the art a reasonable expectation of encapsulating the protein of SEQ ID NO: 1 without inactivating it enzymatically.
With regard to the argument of unexpected results and the argument that the cited prior art does not predict the results found by Applicant, while it is agreed that the specific results disclosed in the specification were not taught or suggested by the cited prior art, one of skill in the art did not need to know these results to find motivation to combine the teachings of the prior art to arrive to the claimed composition. As previously indicated, a person of ordinary skill in the art is motivated to use the dipeptide nanostructures of Marcu et al. to encapsulate the enzyme of Afriat 1 for the benefit of enhancing the stability and storage time of the enzyme of Afriat 1, which is an enzyme that consists of SEQ ID NO: 1, and has the potential of being used as an antimicrobial agent. Moreover, a person of ordinary skill in the art is motivated to use a Tris buffer that comprises Mg divalent ions at a pH between 7-11 because Afriat 1 teaches that the M. tuberculosis PPH in such buffer at a pH of 8-8.5 and in the presence of divalent Mg ions is enzymatically active. A person of ordinary skill in the art is motivated to use a dry form of the composition of Afriat 1 and Marcu et al. for analysis that requires a dry form of the sample. It is reiterated herein that one of ordinary skill in the art had a reasonable expectation of success at encapsulating the protein of Afriat 1 in the nanostructures of Marcu et al. because encapsulation using dipeptide nanostructures have been successfully used as evidenced by Park et al. In addition, one of ordinary skill in the art had a reasonable expectation of success at observing an improved enzymatic stability and storage time in view of the findings of Park et al. with another enzyme that has been encapsulated in dipeptide nanostructures. Therefore, for the reasons of record and those set forth above, one of skill in the art would have to conclude that the claimed invention is obvious over the prior art of record.
Double Patenting
Claims 1-2, 5, 8, 12-15, 31-33 were provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3, 7-12 of copending Application No. 17/596,740 in view of Marcu et al. (U.S. Publication No. 2016/0326215 published 11/10/2016; cited in the IDS), Park et al. (Enzyme and Microbial Technology 51:81-85, 2012; cited in the IDS), and Chen et al. (Int. J. Mol. Sci. 14:17477-17500, 2013).
In view of the fact that the claims have been amended to now require a lactonase that comprises/consists of SEQ ID NO: 1 and the fact that the claims of copending Application No. 17/596,740 require variants of the polypeptide of SEQ ID NO: 1 having specific amino acid substitutions, this rejection is hereby withdrawn.
Conclusion
No claim is in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Applicant is advised that any Internet email communication by the Examiner has to be authorized by Applicant in written form. See MPEP § 502.03 (II). Without a written authorization by Applicant in place, the USPTO will not respond via Internet email to any Internet correspondence which contains information subject to the confidentiality requirement as set forth in 35 U.S.C. 122. Sample written authorization language can be found in MPEP § 502.03 (II). An Authorization for Internet Communications in a Patent Application or Request to Withdraw Authorization for Internet Communications form (SB/439) can be found at https://www.uspto.gov/patent/forms/ forms-patent-applications-filed-or-after-september-16-2012, which can be electronically filed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
June 27, 2026
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