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 27 Jun 2025 is acknowledged. Claims 1-2, 4-13, 15, and 18 are currently pending. Of those, claims 1 and 18 are currently amended, no claims are new and no claims are withdrawn. Claims 3, 14, 16-17, and 19-20 are cancelled. Claims 1-2, 4-13, 15, and 18 will be examined on the merits herein.
Response to Arguments
The Applicants’ arguments filed 27 Jun 2025 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks” and the Non-Final Office Action mailed 31 Mar 2025 will be referred to as “NFOA.”
Objection(s) and Rejection(s) Withdrawn
The objections to the specification and claim 18 are withdrawn in view of the amendments.
The rejection of claim 18 under 35 U.S.C. 112(b) is withdrawn in view of the claim amendments.
The rejection of claims 1-2, 7-13, 15, and 18 under 35 U.S.C. 112(a) is withdrawn in view of the claim amendments and arguments.
Rejection(s) Maintained
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 103
Claims 1-2, 7-9, 11-13, and 18 remain rejected under 35 U.S.C. 103 as being unpatentable over Zollinger (US-20110182942-A1; PTO-892) in view of Gerke et al. (US-20180169206-A1, priority to 15 Jun 2015; hereafter Gerke; PTO-892) and as evidenced by Fisseha et al. (2005; hereafter Fisseha; PTO-892) for the reasons of record and the reasons herein.
Response to Arguments
Applicant argues (Remarks pg. 8) that “Gerke does not teach any heterologous expression of an LpxP enzyme. Instead, Shigella flexneri naturally expresses LpxP and Gerke mentions that this enzyme may compensate for the loss of htrB expression in S. flexneri. Thus, it could not have been reasonably predicted based on the teaching of Gerke that heterologous expression of LpxP in Neisseria would effectively result in neisserial LPS having a palmiteoyl as secondary acyl chain bound to the primary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety.”
This argument has been carefully considered but is not found persuasive. To clarify the record, Gerke was cited to teach “mutant strains with inactivated htrB and expressing LpxP, with the benefit that the lipid A component in LPS is less toxic.” (NFOA par. 29), noting that “Fisseha teaches that lpxL1 corresponds with htrB genes in other organisms” (NFOA par. 28). Applicant has not argued or provided any evidence that heterologous expression of LpxP would cause the enzyme to have a different function in a bacteria compared to endogenous expression. It is also not found persuasive that one of ordinary skill in the art would expect that expressing LpxP in Neisseria specifically (compared to Shigella) would prevent of LpxP from performing its established enzymatic function “that results in hexa-acylated lipid A, wherein the lauroyl-chain is replaced by a palmitoleoyl chain” (NFOA par. 29). It was widely known in the art at the time of filing that enzymes can be moved between different species of bacteria while retaining their function. For example, Gerke teaches that genes from E. coli are functional in Shigella [0021]. Also, Figure 1 of Zariri et al. (2016; PTO-892) shows that one of ordinary skill in the art at the time of filing expected LPS-modifying enzymes including LpxL1 and LpxP to modify Neisserial LPS (see schematic of Figure 1A, and copied in Remarks pg. 9) and including enzymes from non-Neisserial species such as Bordetella bronchiseptica and E. coli (see Figure 1B). Zariri was published several months after the effective filing date, but Figure 1 was cited by the applicant in the Remarks (pg. 9), so it is understood that the applicant considers this portion of the reference relevant to the state of the art at the time of filing. Therefore, applicant’s argument that Gerke’s teaching that a strain with inactivated htrB and expressing LpxP has the benefit that the lipid A component in LPS is less toxic is not relevant to Neisseria because the LpxP would be heterologously expressed is not found persuasive.
Applicant further argues (Remarks pg. 8) that the specification teaches that the introduced LpxP can only add a palmitoleoyl chain to E. coli LPS at 12°C, and the protein is only active at low temperatures. In contrast, the optimal temperature for culturing Neisseria is 35-37°C, so the skilled person would not expect LpxP to be functional when expressed in Neisseria.
This argument has been carefully considered but is not found persuasive. This argument is not commensurate in scope with what is claimed because it is limited to the function of E. coli LpxP when the protein is at low temperatures, but the claim includes the expression of any LpxP and cells grown in any conditions.
Applicant’s conclusion about the expectations of the skilled person are only attorney arguments and do not take the place of evidence in the record. However, a search of the art at the time of filing reveals that one of ordinary skill in the art would have been aware that LpxP is expressed and functional at 30°C (see Mamat et al. 2015; PTO-892; a skilled artisan citing earlier work showing “limited induction of LpxP expression has been demonstrated as a potential compensatory mechanism even at 30°C” in E. coli mutants, pg. 5 col. 2 par. 1) and that N. gonorrhoeae can be grown below the optimal temperature range (see Annear et al., 1982; PTO-892; N. gonorrhoeae growth as low as 25°C, Title). As the known growth range of N. gonorrhoeae overlaps with the known functional range of LpxP, the examiner respectfully disagrees with applicant’s conclusion that the skilled person would not expect E. coli LpxP to be functional when expressed in Neisseria.
Applicant argues (Remarks pg. 8-9) that the configuration of acyl chains differs significantly between S. flexneri and Neisseria, and different penta-acylated strains have different toxicity profiles as shown in Figure 3 of Zariri. “The skilled person knows the importance of the configuration of the acyl chains and would therefore understand that the teachings of Gerke are not relevant for Neisseria.”
This argument has been carefully considered but is not found persuasive. Arguments about the toxicity of penta-acylated LPS don’t appear to be relevant because the claimed invention produces hexa-acylated LPS. Applicant has not cited any sources to support the allegedly different structure of S. flexneri LPS or the expectation that LpxP would have a different enzymatic activity when acting upon those two structures. Applicant is reminded that claim 1 does not require that the LpxP be active, or that the LPS have any particular toxicity profile. Conclusive proof of efficacy is not required to show a reasonable expectation of success. See MPEP 2143.02. The potential for success taught by Gerke is cited as being one motivation for one of ordinary skill in the art to modify Neisseria using known molecular biology techniques and known genetic material.
Claims 1-2, 4-9, 11-13, and 18 remain rejected under 35 U.S.C. 103 as being unpatentable over Zollinger (US-20110182942-A1; PTO-892) in view of Gerke et al. (US-20180169206-A1, priority to 15 Jun 2015; hereafter Gerke; PTO-892) and as evidenced by Fisseha et al. (2005; hereafter Fisseha; PTO-892) as applied to claims 1-2, 7-9, 11-13, and 18 above, and further in view of Lien and Goguen (US-8802419-B2; hereafter Lien; PTO-892) as evidenced by Blattner et al. (GenBank ID AAC75437; 1997) for the reasons of record and the reasons herein.
Response to Arguments
Applicant argues this rejection together with the rejection of Zollinger in view of Gerke and as evidenced by Fisseha above (Remarks pg. 7). This argument has been carefully considered but is not found persuasive for the reasons laid out above.
Claims 1-2, 7, 10-13, 15, and 18 remain rejected under 35 U.S.C. 103 as being unpatentable over Steeghs et al. (US-20080138359-A1; hereafter Steeghs; PTO-892) in view of Gerke et al. (US-20180169206-A1, priority to 15 Jun 2015; hereafter Gerke; PTO-892) for the reasons of record and the reasons herein.
Response to Arguments
Applicant argues this rejection together with the rejection of Zollinger in view of Gerke and as evidenced by Fisseha above (Remarks pg. 9-10). This argument has been carefully considered but is not found persuasive for the reasons laid out above.
Double Patenting
Claims 1-2, 4-13, 15, and 18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 12-17 of U.S. Patent No. 11,292,808 in view of Zollinger et al. (US-20110182942-A1; hereafter Zollinger; PTO-892) for the reasons of record and the reasons herein.
The applicant requested that this rejection be held in abeyance (Remarks pg. 10). The applicant is reminded that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer. Such a response is required even when the nonstatutory double patenting rejection is provisional. See MPEP 804.I.B.1. Also, applicant’s attention is drawn to the fact that this is a rejection over a patent, not a co-pending application.
Claims 1-2, 4-7, 10-13, 15, and 18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-8 of copending Application No. 17/923,257 (reference application) in view of Steeghs et al. (US-20080138359-A1; hereafter Steeghs; PTO-892) and Lien and Goguen (US-8802419-B2; hereafter Lien; PTO-892) as evidenced by Blattner et al. (GenBank ID AAC75437; 1997).
Applicant’s response did not address this rejection (Remarks pg. 10). The applicant is reminded that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer. Such a response is required even when the nonstatutory double patenting rejection is provisional. See MPEP 804.I.B.1.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMELIA NICOLE DICKENS whose telephone number is (571)272-0381. The examiner can normally be reached M-R 8:30-4:30, and every other F 8:30-4:30 (EDT/EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Nickol can be reached at (571)272-0835. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
/GARY B NICKOL/Supervisory Patent Examiner, Art Unit 1645
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