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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 22 Dec 2025 has been entered.
Claim Status
The amended claim set filed 22 Dec 2025 is acknowledged. Claims 1-2, 5-13, 15, and 18 are currently pending. Of those, claim 1 is currently amended, and no claims are new. Claims 3-4, 14, 16-17, and 19-20 are cancelled. Claims 1-2, 5-13, 15, and 18 will be examined on the merits herein.
Response to Arguments
The Applicants’ arguments filed 22 Dec 2025 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks” and the Final Office Action mailed 20 Aug 2025 will be referred to as “FOA.”
Objection(s) and Rejection(s) Withdrawn
The rejection of claims 1-2, 7-9, 11-13, and 18 under 35 U.S.C. 103 over Zollinger in view of Gerke and as evidenced by Fisseha (FOA par. 7-15) is withdrawn in view of the claim amendment to move the limitation from prior claim 4 into independent claim 1, and in view of arguments.
The rejection of claims 1-2, 4-9, 11-13, and 18 under 35 U.S.C. 103 over Zollinger in view of Gerke as evidenced by Fisseha and further in view of Lien as evidenced by Blattner (FOA par. 16-18) is withdrawn in view of arguments and claim amendments. Specifically, the arguments that the immunostimulatory properties of the LPS change depending on the temperature, and that the claims now specify that the bacteria are cultured at a sub-optimal temperature below 35 °C (Remarks pg. 7-8) and that there are significant structural differences between Shigella and Neisseria LPS (Remarks pg. 8) are together persuasive. The teachings of the art at the time of filing does not provide enough motivation to make the many modifications to Zollinger that are required by the instant claims.
The rejection of 1-2, 7, 10-13, 15, and 18 under 35 U.S.C. 103 over Steeghs in view of Gerke (FOA par. 19-21) is withdrawn in view of the claim amendment to move the limitation from prior claim 4 into independent claim 1, and in view of arguments.
The provisional rejection of claims 1-2, 4-7, 10-13, 15, and 18 over claims 7-8 of copending Application No. 17/923,257 (reference application) in view of Steeghs and Lien is withdrawn in view of the claim amendments. There were no arguments presented for this rejection.
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.
Double Patenting
Claims 1-2, 5-13, 15, and 18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 12-17, and 19-20 of U.S. Patent No. 11,292,808, either alone or in view of Zollinger et al. (US-20110182942-A1; hereafter Zollinger; PTO-892) for the reasons of record and the reasons herein.
The prohibition against nonstatutory double patenting rejections under 35 U.S.C. 121 does not apply to the instant divisional application and parent U.S. Patent No. 11,292,808 (Application No. 16/072,895) for at least the following reasons, copied from MPEP 804.01:
(B) The claims of the application under examination and claims of the other application/patent are not consonant with the restriction requirement made by the examiner, since the claims have been changed in material respects from the claims at the time the requirement was made. The elected invention was a genetically modified bacteria, but this was not one of the inventions presented in restriction requirement in Application ‘895 mailed 7 Aug 2019.
(E) The requirement for restriction was withdrawn, in its entirety or in pertinent part, by the examiner before the patent issues. The prior restriction requirement was withdrawn in the notice of allowance in Application ‘895 mailed 26 Nov 2021.
Regarding instant claims 1 and 5-6, ’808 claims 12, 14 and 17 each teach a bacterium of the genus Neisseria, and wherein the bacterium comprises: a) a genetic modification that eliminates the activity of a lipid A biosynthesis lauroyl acyltransferase encoded by an endogenous lpxL1 gene; and, b) a genetic modification that confers to the bacterium lipid A biosynthesis palmitoleoyltransferase activity, wherein the genetic modification introduces the expression of an LpxP lipid A palmitoleyltransferase that has at least 95% amino acid sequence identity with SEQ ID NO: 4. The sequences of the parent ’808 are identical to the instant application. ‘808 claims 14 and 17 teach cultivating a genetically modified bacterium of the genus Neisseria at a temperature in the range of 20-42° C, and dependent claims 19-20 teach the bacterium is cultured at a temperature lower than 37° C. These ranges substantially overlap with the claimed range of less than 35 °C. See MPEP 2144.05: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). … "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). ”
Regarding instant claim 2, ‘808 claim 14 teaches the bacterium is a genetically modified Neisseria meningitidis, Neisseria gonorrhoeae or Neisseria lactamica. Also, ‘808 claims 2-3 teaches that the LPS produced by the methods of claims 12, 14, and 17 include LPS that has the structure of an LPS of a genetically modified Neisseria meningitidis, Neisseria gonorrhoeae or Neisseria lactamica, so the producing bacteria must be from one of those species.
Regarding instant claim 7, ‘808 claim 16 teaches the endogenous lxL1 gene is a gene encoding an LpxL1 protein having an amino acid sequence with at least 90% sequence identity with at least one of SEQ ID NO's: 1-3. The sequences of the parent ’808 are identical to the instant application.
Regarding instant claims 8-9, ‘808 claim 13 teaches that the composition is a whole cell vaccine and the composition optionally further comprises at least one non-neisserial antigen..
Regarding instant claim 10, ‘808 claim 3 teaches that the LPS produced by the methods of claims 12, 14, and 17 include LPS that has the structure of an LPS of a genetically modified Neisseria meningitidis, Neisseria gonorrhoeae or Neisseria lactamica that is at least one of lgtB− and galE−. Therefore, the producing bacteria must have a genetic modification that reduces or eliminates the expression of at least one of the lgtB or galE genes.
Regarding instant claims 13, 15, and 18, ‘808 claims 12, 14 and 17 teach that the bacteria produces LPS of claim 1, which is a neisserial LPS that has a hexa-acylated lipid A moiety, wherein the hexa-acylated lipid A moiety is modified as compared to the lipid A moiety of a wild-type neisserial LPS in that it has a palmitoleoyl (instead of a lauroyl) as secondary acyl chain bound to the primary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. ‘808 claims 2 and 4 teach the identical LPS types as in instant claims 15 and 18.
Claims 1-2, 5-7, 10, 13, 15, and 18 are rejected over the claims of ‘808 alone.
The claims of ‘808 do not teach that the genetically modified bacteria vaccine is further genetically modified to express a heterologous antigen that may be expressed on the extracellular outer membrane surface of the bacterium, as in instant claims 8-9. Also, the claims of ‘808 do not teach that the genetically modified bacteria is N. meningitidis serogroup B, immunotype L3 or strain H44/76 as in instant claims 11-12.
Regarding instant claims 8-9, Zollinger teaches genetically modified strains of Neisseria that provide protective immunity to meningococcal disease that include inactivation of lpxL1 [Abstract, 0008]. The strain comprises “insertion of a second porA gene (subtype P1.7-1,1) in the place of opaD” [0008, 0048]. PorA is a major outer membrane protein [0048], so the heterologous antigen (PorA) is expressed on the extracellular outer membrane surface of the bacterium.
Regarding claims 11-12, the mutant strain is Neisseria meningitidis H44/76, which expresses the antigen with immunotype L3 [Table 9 at 0107].
One of ordinary skill in the art at the time of filing would consider it prima facie obvious to modify the genetically modified lpxL1- lpxP Neisseria bacteria vaccine of the claims of ‘808 by choosing the N. meningitidis strain disclosed in Zollinger and further expressing the antigen PorA, thereby arriving at the claimed invention, because Zollinger teaches that the H44/76 strain is accessible and can be genetically manipulated and because Zollinger teaches that expressing this antigen helps raise immunity against Neisseria. Therefore the combination would be desirable because adding an additional heterologous PorA protein would raise immunity against a broader range of strains and because the genetic modification techniques described in Zollinger are known to be effective in the disclosed strain. See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.” The person of ordinary skill in the art would have had a reasonable expectation of success because genetic manipulation techniques for N. meningitidis were disclosed in Zollinger.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the use of known techniques to improve similar devices, methods or products in the same way is obvious because enhancing a particular class of devices, methods, or products has been made part of the ordinary capabilities of one skilled in the art based upon the teaching of such improvement in other situations. In the instant case, the claims of ‘808 teach a “base” genetically modified Neisseria meningitidis used to make LPS and as a vaccine, and Zollinger teaches a comparable genetically modified Neisseria meningitidis vaccine wherein the use of expressing an additional antigen (PorA) is taught as advantageous and the use of a specific strain (H44/76) is disclosed. Thus, one of ordinary skill in the art could have applied the known technique of Zollinger to the base product taught by the claims of ‘808 to yield predictable results (i.e. the same advantages). Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
MPEP 804 states: “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 in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional.” Applicant did not respond to this rejection (Remarks pg. 9).
Conclusion
No claims are allowed.
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/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
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