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 .
Applicants’ amendment and response of 11/019/2025 is acknowledged.
Status of Claims
Claims 48-58 and 61-69 are pending in this application. Claims 48-56 have been amended. Claims 57-60 have been canceled. New clams 69-69 have been added. Claims 1-47 have been canceled by previous amendment.
Drawings
Applicant’s drawings of 12/12/2022 are acknowledged. The drawings have been accepted by the examiner.
Information Disclosure Statement
6. Applicant’s information disclosure statements of 12/12/2022, 11/28/2023, 5/22/2025, 7/10/2025, 7/19/2025, 9/13/2025, 11/19/2025 are acknowledged. Initialed copies are enclosed. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Election/Restriction
Applicant's election without traverse of 11/19/2025 is acknowledged. The applicant elected group I (claims 48-56 and 68-69 ) which is drawn to an immunogenic composition Claims 61-67 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/19/2025. Claims 48-56 and 68-60 are under consideration.
Claim Objections
Claims 48-56 and 68-60 are objected to because of the following informalities:
The claims contains multiple abbreviations such as Sf2E, Sf3E, Sf6E, GLcNac, PgIB etc. Full name of said abbreviations are required when appears in the claims for the first time. Appropriate correction is required.
Claim Rejections - 35 USC § 103
8. 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.
9. Claims 48-56 and 68-69 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wacker et al., (WO 2014057109 A1) in view of Ravenscroft et al. (Glycobiology vol. 29, no.9. pp.669-681 June 17, 2019) and further in light of GSR309 and BHW49034.
Wacker et al. discloses the bioconjugation of the Shigella flexneri 2a and the S. sonnei (SSsE) O-polysaccharides to asparagine residues introduced into the carrier protein exotoxin A (EPA) from Pseudomonas aeruginosa (see claims 27, 32, 35-41 and fig 26 and para 0053, 00139, 00172, 00183, 00185, 00244, 00245, 00248 and example 6). Wacker et al. which discloses the bioconjugation of the Shigella flexneri 2a and the S. sonnei (SSsE) O-polysaccharides to asparagine residues introduced into the carrier protein exotoxin A (EPA) in E. coli. The bioconjugation of the Shigella flexneri 3a is also mentioned. The difference between the subject-matter of the present Application and Wacker et al. is the amount of different Shigella antigens present in the immunogenic composition. Therefore, the problem to be solved can be formulated as the provision of a multivalent immunogenic composition against different Shigella serotypes. However, in [00244] (p.68) Wacker et al. provides a clear incentive for the proposed solution: "For a comprehensive vaccine against shigellosis using the O antigen polysaccharide as an antigen, it is believed that O antigen structures of at least
five serotypes must be included, to result in sufficient coverage. Wacker et al. teach Sf2a see para 0046, fig 1.
Ravenscroft et al. Abstract recite:
E. coli glycosylation system substantially simplifies the production of a multivalent conjugate vaccine to prevent shigellosis. This bioconjugation approach has been used to produce the Shigella dysenteriae type O1 conjugate that has been successfully tested in a phase 1 clinical study in humans. In this report, we describe a similar approach for the production of additional serotype required for a broadly protective shigellosis vaccine candidate. The Shigella flexneri 2A O-polysaccharide is conjugated to introduced asparagine residue of the carrier protein A (EPA) from Pseudomonas aeruginosa by co-expression with PgIB oligosaccharyltransferase. The bioconjugate was purified .
Ravenscroft et al. teach limitations of claim 55, glycosylation of EPA with S. flexneri 2a O-PS and purification of Sf2a EPA glycoconjugate ( see p 671). Ravenscroft et al. teach Rhamnose, glucose and GlcNAc ( see pages 672,673,676,678). Ravenscroft et al. teach limitations of claim 68 PgIB ( see p 671).
The above references do not teach N-glycosylation and O-glycosylation consensus sequences of claims 49 and 50.
GSR309 teach a sequence 100% identical to SEQ ID NO:31 and BHW49034 teach a sequence 100% identical to SEQ ID NO:29. See sequence alignment below:
Therefore, it would have been prima facie obvious at the time of applicants’ invention to combine the teaching of the above references to obtain instant invention.
Because Wacker et al. discloses the bioconjugation of the Shigella flexneri 2a and the S. sonnei (SSsE) O-polysaccharides to asparagine residues introduced into the carrier protein exotoxin A (EPA) from Pseudomonas aeruginosa (see claims 27, 32, 35-41).
Ravenscroft et al. teach that the Shigella flexneri 2A O-polysaccharide is conjugated to introduced asparagine residue of the carrier protein A (EPA) from Pseudomonas aeruginosa by co-expression with PgIB oligosaccharyltransferase. The bioconjugate was purified . Also Ravenscroft et al. teach glycosylation of EPA with S. flexneri 2a O-PS and purification of Sf2a EPA glycoconjugate ( see p 671). One of the ordinary skill in the art would be motivated to an immunogenic composition comprising Shigella flexneri 2 a O-antigen polysaccharide chains. And produce a tetravalent improved shigellosis vaccine.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known compositions to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known compositions is likely to be obvious when it does no more than yield predictable results". It is well known to adjust the concentration of solution to provide a better method which function in a predictable manner to yield a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
SEQ ID NO:31
RESULT 29
G5R309_SALSE
ID G5R309_SALSE Unreviewed; 30 AA.
AC G5R309;
DT 25-JAN-2012, integrated into UniProtKB/TrEMBL.
DT 25-JAN-2012, sequence version 1.
DT 02-APR-2025, entry version 16.
DE SubName: Full=Uncharacterized protein {ECO:0000313|EMBL:EHC85238.1};
DE Flags: Fragment;
GN ORFNames=LTSESEN_3835 {ECO:0000313|EMBL:EHC85238.1};
OS Salmonella enterica subsp. enterica serovar Senftenberg str. A4-543.
OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria;
OC Enterobacterales; Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=913082 {ECO:0000313|EMBL:EHC85238.1, ECO:0000313|Proteomes:UP000005065};
RN [1] {ECO:0000313|EMBL:EHC85238.1, ECO:0000313|Proteomes:UP000005065}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=A4-543 {ECO:0000313|EMBL:EHC85238.1,
RC ECO:0000313|Proteomes:UP000005065};
RX PubMed=21859443; DOI=10.1186/1471-2164-12-425;
RA den Bakker H.C., Moreno Switt A.I., Govoni G., Cummings C.A., Ranieri M.L.,
RA Degoricija L., Hoelzer K., Rodriguez-Rivera L.D., Brown S., Bolchacova E.,
RA Furtado M.R., Wiedmann M.;
RT "Genome sequencing reveals diversification of virulence factor content and
RT possible host adaptation in distinct subpopulations of Salmonella
RT enterica.";
RL BMC Genomics 12:425-425(2011).
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:EHC85238.1}.
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DR EMBL; AFCU01001258; EHC85238.1; -; Genomic_DNA.
DR AlphaFoldDB; G5R309; -.
DR Proteomes; UP000005065; Unassembled WGS sequence.
PE 4: Predicted;
FT NON_TER 30
FT /evidence="ECO:0000313|EMBL:EHC85238.1"
SQ SEQUENCE 30 AA; 3686 MW; AAB4F6FB7E383E9A CRC64;
Query Match 100.0%; Score 16; Length 30;
Best Local Similarity 60.0%;
Matches 3; Conservative 0; Mismatches 2; Indels 0; Gaps 0;
Qy 1 DXNXS 5
| | |
Db 26 DANSS 30
SEQ ID NO: 29:
RESULT 2
A0A378W1U0_NEIGO
ID A0A378W1U0_NEIGO Unreviewed; 249 AA.
AC A0A378W1U0;
DT 07-NOV-2018, integrated into UniProtKB/TrEMBL.
DT 07-NOV-2018, sequence version 1.
DT 08-OCT-2025, entry version 13.
DE SubName: Full=Large pilS cassette {ECO:0000313|EMBL:SUA25113.1};
GN Name=pilE_4 {ECO:0000313|EMBL:SUA25113.1};
GN ORFNames=NCTC11421_03121 {ECO:0000313|EMBL:SUA25113.1};
OS Neisseria gonorrhoeae.
OC Bacteria; Pseudomonadati; Pseudomonadota; Betaproteobacteria; Neisseriales;
OC Neisseriaceae; Neisseria.
OX NCBI_TaxID=485 {ECO:0000313|EMBL:SUA25113.1};
RN [1] {ECO:0000313|EMBL:SUA25113.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC11421 {ECO:0000313|EMBL:SUA25113.1};
RG Pathogen Informatics;
RA Doyle S.;
RL Submitted (JUN-2018) to the EMBL/GenBank/DDBJ databases.
CC -!- SIMILARITY: Belongs to the N-Me-Phe pilin family.
CC {ECO:0000256|ARBA:ARBA00005233}.
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DR EMBL; UGRI01000001; SUA25113.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A378W1U0; -.
DR GO; GO:0009289; C:pilus; IEA:InterPro.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR Gene3D; 3.30.700.10; Glycoprotein, Type 4 Pilin; 2.
DR InterPro; IPR001082; Pilin.
DR InterPro; IPR045584; Pilin-like.
DR Pfam; PF00114; Pilin; 2.
DR SUPFAM; SSF54523; Pili subunits; 2.
PE 3: Inferred from homology;
SQ SEQUENCE 249 AA; 27137 MW; 92897287E2C92544 CRC64;
Query Match 92.2%; Score 94; Length 249;
Best Local Similarity 94.7%;
Matches 18; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 TWPKDNTSAGVASSPTDIK 19
|||||||||||||| ||||
Db 131 TWPKDNTSAGVASSATDIK 149
Conclusion
10. No claims are allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHATOL S SHAHNAN SHAH whose telephone number is (571)272-0863. The examiner can normally be reached on Mon-Tues , Thurs-Fri 12pm-8pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel E. Kolker can be reached on 3181 The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Khatol S Shahnan-Shah/
Examiner, Art Unit 1645
January 10, 2026
/JANA A HINES/Primary Examiner, Art Unit 1645