DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of Group I in the reply filed on August 10, 2026 is acknowledged.
Claim Amendments
3. The amendment filed August 10, 2026 has been entered. Claims 31, 38, 41 and 43 was currently amended. Claims 1-30 and 45-52 were cancelled. Claims 53-58 were newly added. Claims 31-44 and 53-58 are under consideration in this Office Action.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on August 10, 2026, Jan 7, 2026, Oct 14, 2025 and Sept 10, 2025 were filed. 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 Rejections - 35 USC § 112
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.
5. Claim 31 is 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.
Claim 31 is drawn to a method of treating comprising an administration step. However, the claim does not recite the amount of immunogenic composition needed to administer to an individual. Therefore it is suggested that the claim recite an therapeutically effective amount or similar language with respect to the amount of administration. Clarification is re20180064801uired to overcome the rejection.
Claim Rejections - 35 USC § 103
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
6. Claims 31-34, 37, 39-44 and 56-58 are rejected under 35 U.S.C. 103 as being unpatentable over Poolman et al., (US 20130045231 published 2013-2-21; priority to 2011-03-10) in view of Pizza (US 20180064801 published 2018-03-8; priority to 2017-09-01)
The claims are drawn to a method of treating a meningococcal infection or inducing an immune response against a meningococcus bacterium comprising administering to an individual in need thereof an immunogenic composition comprising a combination of Neisseria meningitidis serogroup B antigens, said combination comprising: (i) at least one factor H binding protein (fHBP) A protein,
(ii) at least one fHBP B protein, (iii) at least one Neisseria adhesin A (NadA) protein, and
(iv) at least one detergent-extracted Outer Membrane Vesicle (dOMV).
Poolman et al., teach treatment or prevention of Neisserial infection and methods for their use and manufacture are provided herein [abstract]. Poolman et al., identifies 2 families of fHbp protein, A and B, and thus allows for the construction of chimeric fHbp fusion proteins with sequences from 2 families, providing protection against Neisseria meningitidis infection or disease [para 62]. The N-terminal fragment from fHbp Family B and F2 C-terminal fragment from fHbp Family A [para 64]. The F1 or F2 portion of the sequence contains epitopes suitable for generation of antibodies against family A and family B fHbp proteins [para 71]. Poolman et al., teach the immunogenic composition of claim 39, wherein the fHbp antigen is selected from: (a) fhBP A, (b) fhBP B, (c) a chimeric protein comprising amino acid sequences F1 and F2, wherein the chimeric protein is capable of eliciting antibodies against both fHbp families; and (d) an immunogenic polypeptide having 95% or greater identity to (a), (b or (c). Poolman et al., teach the first antigen is combined with NadA [para 184-185]. Immunogenic compositions of the disclosure may therefore include combinations of NadA and adhesins where NadA contributes in its capacity as an autotransporter protein. These proteins may be derived from Neisseria meningitidis or Neisseria gonorrhoeae or other Neiserial strains. The disclosure also includes other autotransporter proteins from Neisseria [para 195]. The immunogenic composition further comprises one or more antigens is comprised within an outer membrane vesicle, and wherein the one or more antigens is present in outer membrane vesicle.
In one aspect, where the F1 fragment is from family B, the F1 fragment comprises both Gly at position 121 and Lys at position 122, (numbering based on the MC5-8 strain as a reference family B strain) [para 115]. In one aspect variants would delete residues from between amino acid sequence 52 through to 237 or 54 through to 237, more suitably deleting residues between amino acid 52 through to 133 or 55 through to 133. The mature protein would lack the signal peptide [para 148]. The outer membrane vesicle preparation may be expressed as the full-length protein or suitably as an advantageous variant made up of a fusion of amino acids 1-51 and 134-591 (yielding a mature outer membrane protein of amino acid sequence 134 to the C-terminus)[para 147]. Thus teaching claim 36. In one aspect of the disclosure L2 LOS is combined with fHbp. LPS is suitably presented in an outer membrane vesicle (OMV) (suitably where the vesicle is extracted with a low percentage detergent, more suitably 0.02-0.4%, most suitably deoxycholate [DOC]) but may also be part of a subunit vaccine [para 216]. An outer membrane vesicle may also be prepared via the process of detergent extraction of the bacterial cells (see for example EP 11243) [para 257].
The amount of antigen in each vaccine dose is selected as an amount which induces an immunoprotective response without significant, adverse side effects in typical vaccines. Such amount will vary depending upon which specific immunogen is employed and how it is presented. Generally, it is expected that each dose will comprise 1-100 pg of protein antigen or OMV preparation, suitably 5-50 pg, and most typically in the range 5-25 ug [para 364]. Teaching claim 42.
Therefore, Poolman et al., teach a method of treating a meningococcal infection or inducing an immune response against a meningococcus bacterium comprising administering to an individual in need thereof an immunogenic composition comprising a combination of Neisseria meningitidis serogroup B antigens, said combination comprising: (i) at least one factor H binding protein (fHBP) A protein,
(ii) at least one fHBP B protein, (iii) at least one Neisseria adhesin A (NadA) protein, and
(iv) at least one detergent-extracted Outer Membrane Vesicle (dOMV).
Similarly, Pizza teach Methods and compositions for immunizing a human subject against Neisseria gonorrhoeae [abstract]. The inventors have found that vaccine antigens, including those used in the meningitis B vaccine BEXSERO®, induce bactericidal antibodies against N. gonorrhoeae (NG) [para 32]. Therefore the investors have surprisingly found that meningitis B vaccine BEXSERO® and related vaccines comprising component antigens of BEXSERO® are also expected to provide protection against infection and disease [para 38]. Therefore, as well as being immunized against N. gonorrhoeae, recipients may also be immunized against one or more serogroups of N. meningitidis e.g. one or more of serogroups A, B, C, W135, X and/or Y (even in the absence of capsular saccharides from serogroups A, C, W135 &/or Y) [para 80].
The method for immunizing a human subject in need thereof by administering an immunogenic composition comprising one or more of the following protein antigens: (i) a neisserial Heparin Binding Antigen (NHBA); (ii) a neisserial factor H binding protein (fHbp) antigen; (iii) a neisserial Adhesin A (NadA) antigen; (iv) a neisserial GNA1030 antigen; (v) a neisserial GNA2091 antigen. The composition may further comprise a conjugated capsular saccharide from one or more of meningococcal serogroups A, C, W135 and/or Y [para 9]. As recited by claim 44. The invention provides an immunogenic composition comprising gonococcal Outer Membrane Vesicles (OMVs) and an adjuvant [para 11]. 50 μg of each of NadA and fHbp, adsorbed onto 1.5 mg aluminum hydroxide adjuvant, and with 25 μg OMVs from N. meningitidis strain [para 35]. Thus teaching claim 42
fHbp antigens used with the invention will not be lipidated, and may include amino acid sequences upstream of the natural mature N-terminal cysteine. SEQ ID NOs: 1-3 and 11-12 begin with the cysteine from the natural N-terminus of the relevant mature fHbp polypeptides [para 118]. As recited by claim 32. Compositions used with the invention may also include an fHbp protein that is mutated relative to SEQ ID NO:1, 2 or 3 ( fHbp variant 1, 2 or 3 respectively) to decrease binding to human factor H (fH). Suitable mutations are disclosed in the Rossi reference [para 123]. The fHbp antigen falls into three distinct variants [35] and it has been found that for meningococci, serum raised against a given family is bactericidal within the same family, but is not active against strains which express one of the other two families i.e. there is intra-family cross-protection, but not inter-family cross-protection. The invention can use a single fHbp variant, but to provide broader coverage a composition can usefully include a fHbp from two or three of the variants [para 98].
OMCs may be detergent-extracted OMVs (dOMVs), such as OMVs extracted from cells using deoxycholate treatment [para 133]. As recited by claim 31. Preferred meningococcal OMVs comprise a PorA serotype 1.4. Preferably, the OMVs comprise a PorA variable region epitope 1.7-2 (VR1) and/or 1.4 (VR2) [para 135]. As recited by claims 41 and 56. Compositions may include residual detergent (e.g. deoxycholate) from OMV preparation. The amount of residual detergent is preferably less than 0.4 μg (more preferably less than 0.2 μg) for every μg of meningococcal protein [para 169]. As recited by claim 42. Compositions may include an aluminum salt adjuvant or an oil-in-water emulsion (e.g. a squalene-in-water emulsion). Suitable aluminum salts include hydroxides (e.g. oxyhydroxides), phosphates (e.g. hydroxyphosphates, orthophosphates), or mixtures thereof. A preferred range is between 0.3 and 1 mg/ml. A maximum of 0.85 mg/dose is preferred. Aluminum hydroxide and aluminum phosphate adjuvants are particularly suitable [para 167]. As recited by claims 43, 57-58. The sequence alignments teach claims 34, 36-37, and 39-40.
Alignment of SEQ ID NO:1
ID BFC88682 standard; protein; 261 AA.
AC BFC88682;
XX
DT 03-MAY-2018 (first entry)
XX
DE Neisseria meningitidis factor H binding protein (fHbp), SEQ:11.
XX
KW antibacterial; fHbp antigen; factor H binding protein;
KW neisseria gonorrhoeae infection; vaccine antibacterial.
XX
OS Neisseria meningitidis.
XX
CC PN US2018064801-A1.
CC PD 08-MAR-2018.
CC PF 01-SEP-2017; 2017US-00693663.
PR 02-SEP-2016; 2016US-0383134P.
XX
CC PA (GLAX ) GLAXOSMITHKLINE BIOLOGICALS SA.
CC PI Pizza M;
XX
DR WPI; 2018-188870/20.
XX
CC PT Immunizing a human subject against Neisseria gonorrhoeae, comprises
CC PT administering immunogenic composition comprising at least one protein
CC PT antigen e.g. neisserial heparin binding antigen, and neisserial factor H
CC PT binding protein antigen.
XX
CC PS Claim 10; SEQ ID NO 11; 58pp; English.
XX
CC The present invention relates to a method for immunizing a human subject
CC against Neisseria gonorrhoeae. The method involves administering an
CC immunogenic composition comprising an immunologically effective amount of
CC at least one protein antigen, where the protein antigen is selected from
CC the group consisting of: (i) a neisserial heparin binding antigen (NHBA);
CC (ii) a neisserial factor H binding protein (fHbp) antigen; (iii) a
CC neisserial adhesin A (NadA) antigen; (iv) a neisserial GNA1030 antigen;
CC and (v) a neisserial GNA2091 antigen. The invention further discloses an
CC immunogenic composition comprising gonococcal outer membrane vesicles
CC (OMVs) and an adjuvant. The method of the invention is useful for
CC immunizing the human subject against Neisseria gonorrhoeae. The present
CC sequence represents a Neisseria meningitidis factor H binding protein
CC (fHbp), which is used as a protein antigen in the immunogenic
CC composition.
XX
SQ Sequence 261 AA;
ALIGNMENT:
Query Match 92.4%; Score 1223.5; Length 262;
Best Local Similarity 92.7%;
Matches 243; Conservative 6; Mismatches 12; Indels 1; Gaps 1;
Qy 1 CSS-GSGSGGGGVAADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEK 59
||| | ||||||||||||||||||||||||||||||||||||||| ||||||||||||||
Db 1 CSSGGGGSGGGGVAADIGTGLADALTAPLDHKDKGLKSLTLEDSIPQNGTLTLSAQGAEK 60
Qy 60 TFKVGDKDNSLNTGKLKNDKISRFDFVQKIEVDGQTITLASGEFQIYKQDHSAVVALQIE 119
||| |||||||||||||||||||||||||||||||||||||||||||||:||||||||||
Db 61 TFKAGDKDNSLNTGKLKNDKISRFDFVQKIEVDGQTITLASGEFQIYKQNHSAVVALQIE 120
Qy 120 KINNPDKIDSLINQRSFLVSGLGGEHTAFNQLPSGKAEYHGKAFSSDDAGGKLTYTIDFA 179
||||||| ||||||||||||||||||||||||| |||||||||||||| |:| |:|||
Db 121 KINNPDKTDSLINQRSFLVSGLGGEHTAFNQLPGGKAEYHGKAFSSDDPNGRLHYSIDFT 180
Qy 180 AKQGHGKIEHLKTPEQNVELASAELKADEKSHAVILGDTRYGSEEKGTYHLALFGDRAQE 239
|||:|:|||||| |||||||:||||||||||||||||||||||||||||||||||||||
Db 181 KKQGYGRIEHLKTLEQNVELAAAELKADEKSHAVILGDTRYGSEEKGTYHLALFGDRAQE 240
Qy 240 IAGSATVKIREKVHEIGIAGKQ 261
||||||||| ||||||||||||
Db 241 IAGSATVKIGEKVHEIGIAGKQ 262
SEQ ID NO:2
ID BFC88682 standard; protein; 261 AA.
AC BFC88682;
XX
DT 03-MAY-2018 (first entry)
XX
DE Neisseria meningitidis factor H binding protein (fHbp), SEQ:11.
XX
KW antibacterial; fHbp antigen; factor H binding protein;
KW neisseria gonorrhoeae infection; vaccine antibacterial.
XX
OS Neisseria meningitidis.
XX
CC PN US2018064801-A1.
CC PD 08-MAR-2018.
CC PF 01-SEP-2017; 2017US-00693663.
PR 02-SEP-2016; 2016US-0383134P.
XX
CC PA (GLAX ) GLAXOSMITHKLINE BIOLOGICALS SA.
CC PI Pizza M;
XX
DR WPI; 2018-188870/20.
XX
CC PT Immunizing a human subject against Neisseria gonorrhoeae, comprises
CC PT administering immunogenic composition comprising at least one protein
CC PT antigen e.g. neisserial heparin binding antigen, and neisserial factor H
CC PT binding protein antigen.
XX
CC PS Claim 10; SEQ ID NO 11; 58pp; English.
XX
CC The present invention relates to a method for immunizing a human subject
CC against Neisseria gonorrhoeae. The method involves administering an
CC immunogenic composition comprising an immunologically effective amount of
CC at least one protein antigen, where the protein antigen is selected from
CC the group consisting of: (i) a neisserial heparin binding antigen (NHBA);
CC (ii) a neisserial factor H binding protein (fHbp) antigen; (iii) a
CC neisserial adhesin A (NadA) antigen; (iv) a neisserial GNA1030 antigen;
CC and (v) a neisserial GNA2091 antigen. The invention further discloses an
CC immunogenic composition comprising gonococcal outer membrane vesicles
CC (OMVs) and an adjuvant. The method of the invention is useful for
CC immunizing the human subject against Neisseria gonorrhoeae. The present
CC sequence represents a Neisseria meningitidis factor H binding protein
CC (fHbp), which is used as a protein antigen in the immunogenic
CC composition.
XX
SQ Sequence 261 AA;
Query Match 98.6%; Score 1305; Length 261;
Best Local Similarity 98.9%;
Matches 258; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 1 CSSGSGSGGGGVAADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEKT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CSSGSGSGGGGVAADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEKT 60
Qy 61 FKVGDKDNSLNTGKLKNDKISRFDFVQKIEVDGQTITLASGEFQIYKQDHSAVVALQIEK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FKVGDKDNSLNTGKLKNDKISRFDFVQKIEVDGQTITLASGEFQIYKQDHSAVVALQIEK 120
Qy 121 INNPDKIDSLINQRSFRVSDLGGEHTAFNQLPSGKAEYHGKAFSSDDAGGKLTYTIDFAA 180
|||||||||||||||| || ||||||||||||||||||||||||||||||||||||||||
Db 121 INNPDKIDSLINQRSFLVSGLGGEHTAFNQLPSGKAEYHGKAFSSDDAGGKLTYTIDFAA 180
Qy 181 KQGHGKIEHLKTPEQNVELASAELKADEKSHAVILGDTRYGSEEKSTYHLALFGDRAQEI 240
||||||||||||||||||||||||||||||||||||||||||||| ||||||||||||||
Db 181 KQGHGKIEHLKTPEQNVELASAELKADEKSHAVILGDTRYGSEEKGTYHLALFGDRAQEI 240
Qy 241 AGSATVKIREKVHEIGIAGKQ 261
|||||||||||||||||||||
Db 241 AGSATVKIREKVHEIGIAGKQ 261
Alignment of SEQ ID NO:3
ID BFC88683 standard; protein; 260 AA.
XX
AC BFC88683;
XX
DT 03-MAY-2018 (first entry)
XX
DE Neisseria meningitidis factor H binding protein (fHbp), SEQ:12.
XX
KW antibacterial; fHbp antigen; factor H binding protein;
KW neisseria gonorrhoeae infection; vaccine antibacterial.
XX
OS Neisseria meningitidis.
XX
CC PN US2018064801-A1.
XX
CC PD 08-MAR-2018.
XX
CC PF 01-SEP-2017; 2017US-00693663.
XX
PR 02-SEP-2016; 2016US-0383134P.
XX
CC PA (GLAX ) GLAXOSMITHKLINE BIOLOGICALS SA.
XX
CC PI Pizza M;
XX
DR WPI; 2018-188870/20.
XX
CC PT Immunizing a human subject against Neisseria gonorrhoeae, comprises
CC PT administering immunogenic composition comprising at least one protein
CC PT antigen e.g. neisserial heparin binding antigen, and neisserial factor H
CC PT binding protein antigen.
XX
CC PS Claim 10; SEQ ID NO 12; 58pp; English.
XX
CC The present invention relates to a method for immunizing a human subject
CC against Neisseria gonorrhoeae. The method involves administering an
CC immunogenic composition comprising an immunologically effective amount of
CC at least one protein antigen, where the protein antigen is selected from
CC the group consisting of: (i) a neisserial heparin binding antigen (NHBA);
CC (ii) a neisserial factor H binding protein (fHbp) antigen; (iii) a
CC neisserial adhesin A (NadA) antigen; (iv) a neisserial GNA1030 antigen;
CC and (v) a neisserial GNA2091 antigen. The invention further discloses an
CC immunogenic composition comprising gonococcal outer membrane vesicles
CC (OMVs) and an adjuvant. The method of the invention is useful for
CC immunizing the human subject against Neisseria gonorrhoeae. The present
CC sequence represents a Neisseria meningitidis factor H binding protein
CC (fHbp), which is used as a protein antigen in the immunogenic
CC composition.
XX
SQ Sequence 260 AA;
ALIGNMENT:
Query Match 100.0%; Score 1332; Length 260;
Best Local Similarity 100.0%;
Matches 260; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CSSGGGGSGGGGVTADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CSSGGGGSGGGGVTADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEK 60
Qy 61 TYGNGDSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTALQTEQEQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TYGNGDSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTALQTEQEQ 120
Qy 121 DPEHSEKMVAKRRFRIGDIAGEHTSFDKLPKDVMATYRGTAFGSDDAGGKLTYTIDFAAK 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DPEHSEKMVAKRRFRIGDIAGEHTSFDKLPKDVMATYRGTAFGSDDAGGKLTYTIDFAAK 180
Qy 181 QGHGKIEHLKSPELNVDLAVAYIKPDEKHHAVISGSVLYNQDEKGSYSLGIFGEKAQEVA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QGHGKIEHLKSPELNVDLAVAYIKPDEKHHAVISGSVLYNQDEKGSYSLGIFGEKAQEVA 240
Qy 241 GSAEVETANGIHHIGLAAKQ 260
||||||||||||||||||||
Db 241 GSAEVETANGIHHIGLAAKQ 260
SEQ ID NO:4
BFC88683
ID BFC88683 standard; protein; 260 AA.
XX
AC BFC88683;
XX
DT 03-MAY-2018 (first entry)
XX
DE Neisseria meningitidis factor H binding protein (fHbp), SEQ:12.
XX
KW antibacterial; fHbp antigen; factor H binding protein;
KW neisseria gonorrhoeae infection; vaccine antibacterial.
XX
OS Neisseria meningitidis.
XX
CC PN US2018064801-A1.
XX
CC PD 08-MAR-2018.
XX
CC PF 01-SEP-2017; 2017US-00693663.
XX
PR 02-SEP-2016; 2016US-0383134P.
XX
CC PA (GLAX ) GLAXOSMITHKLINE BIOLOGICALS SA.
XX
CC PI Pizza M;
XX
DR WPI; 2018-188870/20.
XX
CC PT Immunizing a human subject against Neisseria gonorrhoeae, comprises
CC PT administering immunogenic composition comprising at least one protein
CC PT antigen e.g. neisserial heparin binding antigen, and neisserial factor H
CC PT binding protein antigen.
XX
CC PS Claim 10; SEQ ID NO 12; 58pp; English.
XX
CC The present invention relates to a method for immunizing a human subject
CC against Neisseria gonorrhoeae. The method involves administering an
CC immunogenic composition comprising an immunologically effective amount of
CC at least one protein antigen, where the protein antigen is selected from
CC the group consisting of: (i) a neisserial heparin binding antigen (NHBA);
CC (ii) a neisserial factor H binding protein (fHbp) antigen; (iii) a
CC neisserial adhesin A (NadA) antigen; (iv) a neisserial GNA1030 antigen;
CC and (v) a neisserial GNA2091 antigen. The invention further discloses an
CC immunogenic composition comprising gonococcal outer membrane vesicles
CC (OMVs) and an adjuvant. The method of the invention is useful for
CC immunizing the human subject against Neisseria gonorrhoeae. The present
CC sequence represents a Neisseria meningitidis factor H binding protein
CC (fHbp), which is used as a protein antigen in the immunogenic
CC composition.
XX
SQ Sequence 260 AA;
ALIGNMENT:
Query Match 99.5%; Score 1321; Length 260;
Best Local Similarity 99.6%;
Matches 259; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 CSSGGGGSGGGGVTADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CSSGGGGSGGGGVTADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEK 60
Qy 61 TYGNGDSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTALQTEQEQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TYGNGDSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTALQTEQEQ 120
Qy 121 DPEHSEKMVAKRRFRIGDIAGEHTSFDKLPKDVMATYRGTAFGSDDAGGKLTYTIDFAAK 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DPEHSEKMVAKRRFRIGDIAGEHTSFDKLPKDVMATYRGTAFGSDDAGGKLTYTIDFAAK 180
Qy 181 QGHGKIEHLKSPELNVDLAVAYIKPDEKHHAVISGSVLYNQDEKGSYSLGIFGEKAQEVA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QGHGKIEHLKSPELNVDLAVAYIKPDEKHHAVISGSVLYNQDEKGSYSLGIFGEKAQEVA 240
Qy 241 GSAEVETANGIHLIGLAAKQ 260
|||||||||||| |||||||
Db 241 GSAEVETANGIHHIGLAAKQ 260
SEQ ID NO:5
ID BFC88676 standard; protein; 364 AA.
XX
AC BFC88676;
XX
DT 03-MAY-2018 (first entry)
XX
DE Neisseria meningitidis MC58 neisserial adhesin A (NadA) antigen, SEQ:5.
XX
KW NadA antigen; antibacterial; neisseria gonorrhoeae infection;
KW vaccine antibacterial.
XX
OS Neisseria meningitidis MC58.
XX
CC PN US2018064801-A1.
XX
CC PD 08-MAR-2018.
XX
CC PF 01-SEP-2017; 2017US-00693663.
XX
PR 02-SEP-2016; 2016US-0383134P.
XX
CC PA (GLAX ) GLAXOSMITHKLINE BIOLOGICALS SA.
XX
CC PI Pizza M;
XX
DR WPI; 2018-188870/20.
DR NCBI; Gi7227256.
XX
CC PT Immunizing a human subject against Neisseria gonorrhoeae, comprises
CC PT administering immunogenic composition comprising at least one protein
CC PT antigen e.g. neisserial heparin binding antigen, and neisserial factor H
CC PT binding protein antigen.
XX
CC PS Claim 10; SEQ ID NO 5; 58pp; English.
XX
CC The present invention relates to a method for immunizing a human subject
CC against Neisseria gonorrhoeae. The method involves administering an
CC immunogenic composition comprising an immunologically effective amount of
CC at least one protein antigen, where the protein antigen is selected from
CC the group consisting of: (i) a neisserial heparin binding antigen (NHBA);
CC (ii) a neisserial factor H binding protein (fHbp) antigen; (iii) a
CC neisserial adhesin A (NadA) antigen; (iv) a neisserial GNA1030 antigen;
CC and (v) a neisserial GNA2091 antigen. The invention further discloses an
CC immunogenic composition comprising gonococcal outer membrane vesicles
CC (OMVs) and an adjuvant. The method of the invention is useful for
CC immunizing the human subject against Neisseria gonorrhoeae. The present
CC sequence represents a Neisseria meningitidis MC58 neisserial adhesin A
CC (NadA) antigen, which is used as a protein antigen in the immunogenic
CC composition.
XX
SQ Sequence 364 AA;
Query Match 99.6%; Score 1383; Length 364;
Best Local Similarity 100.0%;
Matches 283; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 TSDDDVKKAATVAIVAAYNNGQEINGFKAGETIYDIGEDGTITQKDATAADVEADDFKGL 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 27 TSDDDVKKAATVAIVAAYNNGQEINGFKAGETIYDIGEDGTITQKDATAADVEADDFKGL 86
Qy 62 GLKKVVTNLTKTVNENKQNVDAKVKAAESEIEKLTTKLADTDAALADTDAALDETTNALN 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 87 GLKKVVTNLTKTVNENKQNVDAKVKAAESEIEKLTTKLADTDAALADTDAALDETTNALN 146
Qy 122 KLGENITTFAEETKTNIVKIDEKLEAVADTVDKHAEAFNDIADSLDETNTKADEAVKTAN 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 147 KLGENITTFAEETKTNIVKIDEKLEAVADTVDKHAEAFNDIADSLDETNTKADEAVKTAN 206
Qy 182 EAKQTAEETKQNVDAKVKAAETAAGKAEAAAGTANTAADKAEAVAAKVTDIKADIATNKA 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 207 EAKQTAEETKQNVDAKVKAAETAAGKAEAAAGTANTAADKAEAVAAKVTDIKADIATNKA 266
Qy 242 DIAKNSARIDSLDKNVANLRKETRQGLAEQAALSGLFQPYNVG 284
|||||||||||||||||||||||||||||||||||||||||||
Db 267 DIAKNSARIDSLDKNVANLRKETRQGLAEQAALSGLFQPYNVG 309
SEQ ID NO:6
BFC88672
ID BFC88672 standard; protein; 255 AA.
XX
AC BFC88672;
XX
DT 03-MAY-2018 (first entry)
XX
DE Neisseria meningitidis MC58 factor H binding protein (fHbp), SEQ:1.
XX
KW antibacterial; fHbp antigen; neisseria gonorrhoeae infection;
KW vaccine antibacterial.
XX
OS Neisseria meningitidis MC58.
XX
CC PN US2018064801-A1.
XX
CC PD 08-MAR-2018.
XX
CC PF 01-SEP-2017; 2017US-00693663.
XX
PR 02-SEP-2016; 2016US-0383134P.
XX
CC PA (GLAX ) GLAXOSMITHKLINE BIOLOGICALS SA.
XX
CC PI Pizza M;
XX
DR WPI; 2018-188870/20.
XX
CC PT Immunizing a human subject against Neisseria gonorrhoeae, comprises
CC PT administering immunogenic composition comprising at least one protein
CC PT antigen e.g. neisserial heparin binding antigen, and neisserial factor H
CC PT binding protein antigen.
XX
CC PS Claim 10; SEQ ID NO 1; 58pp; English.
XX
CC The present invention relates to a method for immunizing a human subject
CC against Neisseria gonorrhoeae. The method involves administering an
CC immunogenic composition comprising an immunologically effective amount of
CC at least one protein antigen, where the protein antigen is selected from
CC the group consisting of: (i) a neisserial heparin binding antigen (NHBA);
CC (ii) a neisserial factor H binding protein (fHbp) antigen; (iii) a
CC neisserial adhesin A (NadA) antigen; (iv) a neisserial GNA1030 antigen;
CC and (v) a neisserial GNA2091 antigen. The invention further discloses an
CC immunogenic composition comprising gonococcal outer membrane vesicles
CC (OMVs) and an adjuvant. The method of the invention is useful for
CC immunizing the human subject against Neisseria gonorrhoeae. The present
CC sequence represents a Neisseria meningitidis MC58 factor H binding
CC protein (fHbp), which is used as a protein antigen in the immunogenic
CC composition.
XX
SQ Sequence 255 AA;
ALIGNMENT:
Query Match 100.0%; Score 1294; Length 255;
Best Local Similarity 100.0%;
Matches 255; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CSSGGGGVAADIGAGLADALTAPLDHKDKGLQSLTLDQSVRKNEKLKLAAQGAEKTYGNG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CSSGGGGVAADIGAGLADALTAPLDHKDKGLQSLTLDQSVRKNEKLKLAAQGAEKTYGNG 60
Qy 61 DSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTAFQTEQIQDSEHS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTAFQTEQIQDSEHS 120
Qy 121 GKMVAKRQFRIGDIAGEHTSFDKLPEGGRATYRGTAFGSDDAGGKLTYTIDFAAKQGNGK 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GKMVAKRQFRIGDIAGEHTSFDKLPEGGRATYRGTAFGSDDAGGKLTYTIDFAAKQGNGK 180
Qy 181 IEHLKSPELNVDLAAADIKPDGKRHAVISGSVLYNQAEKGSYSLGIFGGKAQEVAGSAEV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 IEHLKSPELNVDLAAADIKPDGKRHAVISGSVLYNQAEKGSYSLGIFGGKAQEVAGSAEV 240
Qy 241 KTVNGIRHIGLAAKQ 255
|||||||||||||||
Db 241 KTVNGIRHIGLAAKQ 255
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Pizza non-lipidated fHbp antigen; NadA antigen; detergent extracted OMvs to Poolman’s composition already comprising FHbp A and B protein antigens, NadA, OMV, in order to provide a composition that elicts an immune response against both Neisseria meningitidis, Neisseria gonorrhoeae or other Neiserial infections. One of ordinary skill in the art would have a reasonable expectation of success by incorporating the well-known A and B antigens would provide protection beyond serogroup A or B alone, thus such universal protection is not the normal standard in this field. Furthermore, no more than routine skill would have been required to incorporate the both fHbp A and B of Poolman et al., because the fHbp antigen falls into three distinct variants and it has been found that for meningococci, serum raised against a given family is bactericidal within the same family, but is not active against strains which express one of the other two families i.e. there is intra-family cross-protection, but not inter-family cross-protection. Thus a single fHbp variant, does not provide broader coverage from two or three of the variants.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods 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 methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of treating a meningococcal infection or inducing an immune response against a meningococcus bacterium in a subject, comprising administering to the subject a therapeutically effective amount of a fHBP A and B protein, a NadA protein and an OMV , wherein there is no change in the respective function of the proteins or vesicles, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, 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.
Claim Rejections - 35 USC § 103
7. Claims 35-36, 38 and 53-55 are rejected under 35 U.S.C. 103 as being unpatentable over Poolman et al., and Pizza as applied to claims 31-34, 37, 39-44 and 56-58 above, and further in view of Rossi et al., (ASM Journals. Infect & Immun. Vol.84, No. 6. 24 May 2016).
Poolman et al., and Pizza have been discussed above as teaching a method of treating a meningococcal infection or inducing an immune response against a meningococcus bacterium comprising administering to an individual in need thereof an immunogenic composition comprising a combination of Neisseria meningitidis serogroup B antigens, said combination comprising: (i) at least one factor H binding protein (fHBP) A protein, (ii) at least one fHBP B protein, (iii) at least one Neisseria adhesin A (NadA) protein, and (iv) at least one detergent-extracted Outer Membrane Vesicle (dOMV). Pizza teach compositions may also include an fHbp protein that is mutated relative to SEQ ID NO:1, 2 or 3 ( fHbp variant 1, 2 or 3 respectively) to decrease binding to human factor H (fH). Suitable mutations are disclosed in the incorporated Rossi reference [para 123 of Pizza]. However neither the instantly recited mutations.
Rossi et al., teach Factor H binding protein (FHbp) is a component of two licensed meningococcal serogroup B vaccines. FHbp recruits the complement regulator factor H (FH) to the bacterial surface, which inhibits the complement alternative pathway and promotes immune evasion. Binding of human FH impairs the protective antibody responses to FHbp, and mutation of FHbp to decrease binding of FH can increase the protective responses [Abstract]. Rossi et al., previously stabilized an FHbp variant group 2 protein by replacement of two amino acid residues, L130 and G133, with their counterparts, R130 and D133, from a variant group 1 protein. The L130R G133D double mutant had 21°C-higher thermal stability of the N-terminal domain and 7-fold-decreased binding of human FH compared to the wild-type [Introduction]. Rossi et al., generated four new FHbp single mutants that decreased FH binding and retained binding of anti-FHbp MAbs and immunogenicity in wild-type mice. From these mutants, we selected two, K219N and G220S, to combine with the stabilized double-mutant FHbp antigen. The two triple mutants decreased FH binding >200-fold, increased the thermal stability of the N-terminal domain by 21°C, and bound better to an anti-FHbp MAb than the wild-type FHbp. In human-FH-transgenic mice, the FHbp triple mutants elicited 8- to 15-fold-higher protective antibody responses than the wild-type FHbp antigen. Collectively, the data suggest that mutations to eliminate binding of human FH and to promote conformational stability act synergistically to optimize FHbp immunogenicity [Abstract]. Table 1 shows FHbp variants include F129S, L130R, G133D, K219N, G220S.
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Rossi’s fHbp mutants to the composition as taught by Poolman et al and Pizza in order to expand the cross protection and against diverse meningococcal strains. One of ordinary skill in the art would have a reasonable expectation of success by incorporating the mutant fHbp antigens which provide higher thermal stability of the N-terminal domain and 7-fold-decreased binding of human FH compared to the wild-type FHbp. Furthermore, no more than routine skill would have been required to incorporate the fHbp mutants as taught by Pizza and Rossi et al., because they teach increase FHbp stability with new, additional single-amino-acid substitutions to decrease further binding of human FH to FHbp antigens. Collectively the data show the vaccine potential of several novel FHbp mutants, which could be combined with other FHbp sequence variants or other meningococcal antigens to increase the protective antibody responses to maximize the breadth of protection against meningococci.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods 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 methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of treating a meningococcal infection or inducing an immune response against a meningococcus bacterium in a subject, comprising administering to the subject a therapeutically effective amount of a fHBP A and B protein, a NadA protein and an OMV; wherein there is no change in the respective function of the proteins or vesicles, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, 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.
Pertinent Art
8. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
Zlotnick et al., (WO 2003063766) teach SEQ ID NO:1 (100%), SEQ ID NO:2 (98.6%), SEQ ID NO:3 (100%), SEQ ID NO:4 (99.5%), and SEQ ID NO:6 (99.5%).
Anderson et al., (WO 2012032489) teach SEQ ID NO:1 (99.3%), SEQ ID NO:2 (98.0%), SEQ ID NO:3 (99.3%), SEQ ID NO:4 (98.8%), and SEQ ID NO:6 (99.3%).
Anderson et al., teach non-lipidated fHBP proteins elicit a bactericidal immune response in a mammal against an ORF2086 subfamily B polypeptide from serogroup B Neisseria meningitidis, and methods related thereto.
Murphy et al., (Journal of Infectious Diseases . Vol. 200, pp.379-389, 2009) teach sequence diversity of fHBP protein vaccine candidates in serogroup B of Neisseria meningitis (see title). Murphy et al. teach fHBP A and fHBP B as vaccine candidate (see background and results summary). Murphy et al. teach a sequence 100% identical to G220S substitution based on the numbering of SEQ ID NO:6.
Arico et al., (WO 2011161653 published 2011-12-29; priority to June 25, 2010).Arico et al., teach administration to patients are immunogenic, and are more preferably vaccine compositions. Vaccines according to the invention may either be prophylactic (i.e. to prevent infection) or therapeutic (i.e. to treat infection), but will typically be prophylactic. Immunogenic compositions used as vaccines comprise an immunologically effective amount of antigen(s), as well as any other components, as needed [para 153]. Compositions of the invention include at least two different meningococcal factor H binding proteins (fHbp) to generate distinct immune responses which are not fully cross-reactive and which provide a broader spectrum of strain coverage against meningococci that the single fHbps alone [para 12]. The fHbp antigen(s) are not lapidated [para 36]. Thus a composition may include a polypeptide antigen NadA [para 90]. The most useful NadA antigens of the invention can elicit antibodies which, after administration to a subject, can bind to a meningococcal polypeptide consisting of amino acid sequence SEQ ID NO: 10. Advantageous NadA antigens for use with the invention can elicit bactericidal anti-meningococcal antibodies after administration to a subject. SEQ ID NO: 6 is one such fragment [para 92]. In addition to including meningococcal fHbp antigens, a composition may include one or more meningococcal capsular saccharide conjugates. A composition of the invention may include one or more conjugates of capsular saccharides from 1, 2, 3, or 4 of meningococcal serogroups A, C, W135 and Y [para 107]. Thus teaching claim 44.
The immune response is preferably protective against meningococcus and preferably involves antibodies. The method may raise a booster response in a patient that has already been primed [para 157]. These uses and methods are preferably for the prevention and/or treatment of a disease caused by N. meningitidis e.g. bacterial (or, more specifically, meningococcal) meningitis, or septicemia [para 161]. Antigens and adjuvants in a composition will typically be in admixture at the time of delivery to a patient. The emulsions may be mixed with antigen during manufacture, or extemporaneously, at the time of delivery. Thus the adjuvant and antigen may be kept separately in a packaged or distributed vaccine, ready for final formulation at the time of use [para 68]. Where a composition is adjuvanted, it may include e.g. an aluminum salt adjuvant, an oil-in-water emulsion adjuvant, or an immunostimulatory oligonucleotide adjuvant. Suitable aluminum salts include aluminum hydroxide. Thus teaching claims 57-58.
Alignment with instantly recited SEQ ID NO:1
AZR46704
ID AZR46704 standard; protein; 261 AA.
AC AZR46704;
XX
DT 16-FEB-2012 (first entry)
XX
DE N. meningitidis strain MC58 fHbp protein (second antigen), SEQ ID 25.
XX
KW Factor H binding protein; antibacterial; antigen; fHbp protein;
KW immune stimulation; immunogenicity; neisseria meningitidis infection;
KW prophylactic to disease; therapeutic; vaccine antibacterial;
KW vaccine, general; BOND_PC; putative lipoprotein precursor;
KW putative lipoprotein; lipoprotein precursor; lipoprotein.
XX
OS Neisseria meningitidis MC58.
XX
CC PN WO2011161653-A1.
CC PD 29-DEC-2011.
CC PF 24-JUN-2011; 2011WO-IB052785.
PR 25-JUN-2010; 2010US-0358816P.
XX
CC PA (NOVS ) NOVARTIS AG.
XX
CC PI Arico BM, Brunelli B, Comanducci M, Pizza M, Savino S;
CC PI Scarselli M;
XX
DR WPI; 2012-A08202/04.
DR PC:NCBI; gi40353389.
XX
CC PT Immunogenic composition useful for treating a disease caused by Neisseria
CC PT meningitidis comprises two different meningococcal factor H binding
CC PT proteins.
XX
CC PS Claim 2; SEQ ID NO 25; 41pp; English.
XX
CC The present invention relates to a novel immunogenic composition
CC (vaccine) comprising two different Meningococcal factor H binding protein
CC (fHbp) antigens. Polypeptides and polynucleotides of the invention are
CC used in the immunogenic composition for treating disease caused by
CC Neisseria meningitidis. The immunogenic composition of the invention
CC useful for raising an immune response against meningococcus. The
CC immunogenic composition can also be used for preventing or treating
CC disease caused by Neisseria meningitidis. The present sequence is a N.
CC meningitidis strain MC58 fHbp antigen (second antigen) used in the
CC composition, of the invention.
CC
CC Revised record issued on 03-FEB-2012 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 261 AA;
ALIGNMENT:
Query Match 100.0%; Score 1324; Length 261;
Best Local Similarity 100.0%;
Matches 261; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CSSGSGSGGGGVAADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEKT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CSSGSGSGGGGVAADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEKT 60
Qy 61 FKVGDKDNSLNTGKLKNDKISRFDFVQKIEVDGQTITLASGEFQIYKQDHSAVVALQIEK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FKVGDKDNSLNTGKLKNDKISRFDFVQKIEVDGQTITLASGEFQIYKQDHSAVVALQIEK 120
Qy 121 INNPDKIDSLINQRSFLVSGLGGEHTAFNQLPSGKAEYHGKAFSSDDAGGKLTYTIDFAA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 INNPDKIDSLINQRSFLVSGLGGEHTAFNQLPSGKAEYHGKAFSSDDAGGKLTYTIDFAA 180
Qy 181 KQGHGKIEHLKTPEQNVELASAELKADEKSHAVILGDTRYGSEEKGTYHLALFGDRAQEI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 KQGHGKIEHLKTPEQNVELASAELKADEKSHAVILGDTRYGSEEKGTYHLALFGDRAQEI 240
Qy 241 AGSATVKIREKVHEIGIAGKQ 261
|||||||||||||||||||||
Db 241 AGSATVKIREKVHEIGIAGKQ 261
Alignment with instantly recited SEQ ID NO:2
AZR46704
ID AZR46704 standard; protein; 261 AA.
AC AZR46704;
XX
DT 16-FEB-2012 (first entry)
XX
DE N. meningitidis strain MC58 fHbp protein (second antigen), SEQ ID 25.
XX
KW Factor H binding protein; antibacterial; antigen; fHbp protein;
KW immune stimulation; immunogenicity; neisseria meningitidis infection;
KW prophylactic to disease; therapeutic; vaccine antibacterial;
KW vaccine, general; BOND_PC; putative lipoprotein precursor;
KW putative lipoprotein; lipoprotein precursor; lipoprotein.
XX
OS Neisseria meningitidis MC58.
XX
CC PN WO2011161653-A1.
CC PD 29-DEC-2011.
CC PF 24-JUN-2011; 2011WO-IB052785.
PR 25-JUN-2010; 2010US-0358816P.
XX
CC PA (NOVS ) NOVARTIS AG.
XX
CC PI Arico BM, Brunelli B, Comanducci M, Pizza M, Savino S;
CC PI Scarselli M;
XX
DR WPI; 2012-A08202/04.
DR PC:NCBI; gi40353389.
XX
CC PT Immunogenic composition useful for treating a disease caused by Neisseria
CC PT meningitidis comprises two different meningococcal factor H binding
CC PT proteins.
XX
CC PS Claim 2; SEQ ID NO 25; 41pp; English.
XX
CC The present invention relates to a novel immunogenic composition
CC (vaccine) comprising two different Meningococcal factor H binding protein
CC (fHbp) antigens. Polypeptides and polynucleotides of the invention are
CC used in the immunogenic composition for treating disease caused by
CC Neisseria meningitidis. The immunogenic composition of the invention
CC useful for raising an immune response against meningococcus. The
CC immunogenic composition can also be used for preventing or treating
CC disease caused by Neisseria meningitidis. The present sequence is a N.
CC meningitidis strain MC58 fHbp antigen (second antigen) used in the
CC composition, of the invention.
ALIGNMENT:
Query Match 98.6%; Score 1305; Length 261;
Best Local Similarity 98.9%;
Matches 258; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 1 CSSGSGSGGGGVAADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEKT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CSSGSGSGGGGVAADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEKT 60
Qy 61 FKVGDKDNSLNTGKLKNDKISRFDFVQKIEVDGQTITLASGEFQIYKQDHSAVVALQIEK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FKVGDKDNSLNTGKLKNDKISRFDFVQKIEVDGQTITLASGEFQIYKQDHSAVVALQIEK 120
Qy 121 INNPDKIDSLINQRSFRVSDLGGEHTAFNQLPSGKAEYHGKAFSSDDAGGKLTYTIDFAA 180
|||||||||||||||| || ||||||||||||||||||||||||||||||||||||||||
Db 121 INNPDKIDSLINQRSFLVSGLGGEHTAFNQLPSGKAEYHGKAFSSDDAGGKLTYTIDFAA 180
Qy 181 KQGHGKIEHLKTPEQNVELASAELKADEKSHAVILGDTRYGSEEKSTYHLALFGDRAQEI 240
||||||||||||||||||||||||||||||||||||||||||||| ||||||||||||||
Db 181 KQGHGKIEHLKTPEQNVELASAELKADEKSHAVILGDTRYGSEEKGTYHLALFGDRAQEI 240
Qy 241 AGSATVKIREKVHEIGIAGKQ 261
|||||||||||||||||||||
Db 241 AGSATVKIREKVHEIGIAGKQ 261
Alignment with instantly recited SEQ ID NO:3
AZR46702
ID AZR46702 standard; protein; 260 AA.
AC AZR46702;
XX
DT 16-FEB-2012 (first entry)
XX
DE N. meningitidis strain M01573 fHbp protein (first antigen), SEQ ID 23.
XX
KW Factor H binding protein; antibacterial; antigen; fHbp protein;
KW immune stimulation; immunogenicity; neisseria meningitidis infection;
KW prophylactic to disease; therapeutic; vaccine antibacterial;
KW vaccine, general; BOND_PC; lipoprotein precursor; lipoprotein.
XX
OS Neisseria meningitidis; M01573.
XX
CC PN WO2011161653-A1.
CC PD 29-DEC-2011.
CC PF 24-JUN-2011; 2011WO-IB052785.
PR 25-JUN-2010; 2010US-0358816P.
XX
CC PA (NOVS ) NOVARTIS AG.
XX
CC PI Arico BM, Brunelli B, Comanducci M, Pizza M, Savino S;
CC PI Scarselli M;
XX
DR WPI; 2012-A08202/04.
DR NCBI; gi40353481.
DR PC:NCBI; gi40353481.
XX
CC PT Immunogenic composition useful for treating a disease caused by Neisseria
CC PT meningitidis comprises two different meningococcal factor H binding
CC PT proteins.
XX
CC PS Claim 1; SEQ ID NO 23; 41pp; English.
XX
CC The present invention relates to a novel immunogenic composition
CC (vaccine) comprising two different Meningococcal factor H binding protein
CC (fHbp) antigens. Polypeptides and polynucleotides of the invention are
CC used in the immunogenic composition for treating disease caused by
CC Neisseria meningitidis. The immunogenic composition of the invention
CC useful for raising an immune response against meningococcus. The
CC immunogenic composition can also be used for preventing or treating
CC disease caused by Neisseria meningitidis. The present sequence is a N.
CC meningitidis strain M01573 fHbp antigen (first antigen) used in the
CC composition, of the invention.
ALIGNMENT:
Query Match 100.0%; Score 1332; Length 260;
Best Local Similarity 100.0%;
Matches 260; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CSSGGGGSGGGGVTADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CSSGGGGSGGGGVTADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEK 60
Qy 61 TYGNGDSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTALQTEQEQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TYGNGDSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTALQTEQEQ 120
Qy 121 DPEHSEKMVAKRRFRIGDIAGEHTSFDKLPKDVMATYRGTAFGSDDAGGKLTYTIDFAAK 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DPEHSEKMVAKRRFRIGDIAGEHTSFDKLPKDVMATYRGTAFGSDDAGGKLTYTIDFAAK 180
Qy 181 QGHGKIEHLKSPELNVDLAVAYIKPDEKHHAVISGSVLYNQDEKGSYSLGIFGEKAQEVA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QGHGKIEHLKSPELNVDLAVAYIKPDEKHHAVISGSVLYNQDEKGSYSLGIFGEKAQEVA 240
Qy 241 GSAEVETANGIHHIGLAAKQ 260
||||||||||||||||||||
Db 241 GSAEVETANGIHHIGLAAKQ 260
Alignment with instantly recited SEQ ID NO:4
AZR46702
ID AZR46702 standard; protein; 260 AA.
AC AZR46702;
XX
DT 16-FEB-2012 (first entry)
XX
DE N. meningitidis strain M01573 fHbp protein (first antigen), SEQ ID 23.
XX
KW Factor H binding protein; antibacterial; antigen; fHbp protein;
KW immune stimulation; immunogenicity; neisseria meningitidis infection;
KW prophylactic to disease; therapeutic; vaccine antibacterial;
KW vaccine, general; BOND_PC; lipoprotein precursor; lipoprotein.
XX
OS Neisseria meningitidis; M01573.
XX
CC PN WO2011161653-A1.
CC PD 29-DEC-2011.
CC PF 24-JUN-2011; 2011WO-IB052785.
PR 25-JUN-2010; 2010US-0358816P.
XX
CC PA (NOVS ) NOVARTIS AG.
XX
CC PI Arico BM, Brunelli B, Comanducci M, Pizza M, Savino S;
CC PI Scarselli M;
XX
DR WPI; 2012-A08202/04.
DR NCBI; gi40353481.
DR PC:NCBI; gi40353481.
XX
CC PT Immunogenic composition useful for treating a disease caused by Neisseria
CC PT meningitidis comprises two different meningococcal factor H binding
CC PT proteins.
XX
CC PS Claim 1; SEQ ID NO 23; 41pp; English.
XX
CC The present invention relates to a novel immunogenic composition
CC (vaccine) comprising two different Meningococcal factor H binding protein
CC (fHbp) antigens. Polypeptides and polynucleotides of the invention are
CC used in the immunogenic composition for treating disease caused by
CC Neisseria meningitidis. The immunogenic composition of the invention
CC useful for raising an immune response against meningococcus. The
CC immunogenic composition can also be used for preventing or treating
CC disease caused by Neisseria meningitidis. The present sequence is a N.
CC meningitidis strain M01573 fHbp antigen (first antigen) used in the
CC composition, of the invention.
ALIGNMENT:
Query Match 99.5%; Score 1321; Length 260;
Best Local Similarity 99.6%;
Matches 259; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 CSSGGGGSGGGGVTADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CSSGGGGSGGGGVTADIGTGLADALTAPLDHKDKGLKSLTLEDSISQNGTLTLSAQGAEK 60
Qy 61 TYGNGDSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTALQTEQEQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TYGNGDSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTALQTEQEQ 120
Qy 121 DPEHSEKMVAKRRFRIGDIAGEHTSFDKLPKDVMATYRGTAFGSDDAGGKLTYTIDFAAK 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DPEHSEKMVAKRRFRIGDIAGEHTSFDKLPKDVMATYRGTAFGSDDAGGKLTYTIDFAAK 180
Qy 181 QGHGKIEHLKSPELNVDLAVAYIKPDEKHHAVISGSVLYNQDEKGSYSLGIFGEKAQEVA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QGHGKIEHLKSPELNVDLAVAYIKPDEKHHAVISGSVLYNQDEKGSYSLGIFGEKAQEVA 240
Qy 241 GSAEVETANGIHLIGLAAKQ 260
|||||||||||| |||||||
Db 241 GSAEVETANGIHHIGLAAKQ 260
Alignment with instantly recited SEQ ID NO:5
ID AZR46689 standard; protein; 364 AA.
AC AZR46689;
XX
DT 16-FEB-2012 (first entry)
DE N. meningitidis strain MC58 NadA antigen, SEQ ID 10.
XX
KW NadA; antibacterial; antigen; immune stimulation; immunogenicity;
KW neisseria meningitidis infection; prophylactic to disease; therapeutic;
KW vaccine antibacterial; vaccine, general; BOND_PC;
KW adhesin/invasin, putative; putative adhesin/invasin; GO5215; GO6810.
XX
OS Neisseria meningitidis MC58.
XX
CC PN WO2011161653-A1.
CC PD 29-DEC-2011.
CC PF 24-JUN-2011; 2011WO-IB052785.
PR 25-JUN-2010; 2010US-0358816P.
XX
CC PA (NOVS ) NOVARTIS AG.
XX
CC PI Arico BM, Brunelli B, Comanducci M, Pizza M, Savino S;
CC PI Scarselli M;
XX
DR WPI; 2012-A08202/04.
DR NCBI; gi7227256.
DR PC:NCBI; gi15677822.
XX
CC PT Immunogenic composition useful for treating a disease caused by Neisseria
CC PT meningitidis comprises two different meningococcal factor H binding
CC PT proteins.
XX
CC PS Disclosure; SEQ ID NO 10; 41pp; English.
XX
CC The present invention relates to a novel immunogenic composition
CC (vaccine) comprising two different Meningococcal factor H binding protein
CC (fHbp) antigens. Polypeptides and polynucleotides of the invention are
CC used in the immunogenic composition for treating disease caused by
CC Neisseria meningitidis. The immunogenic composition of the invention
CC useful for raising an immune response against meningococcus. The
CC immunogenic composition can also be used for preventing or treating
CC disease caused by Neisseria meningitidis. The present sequence is a N.
CC meningitidis strain MC58 NadA antigen used in the immunogenic
CC composition, of the invention.
CC
CC Revised record issued on 03-FEB-2012 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 364 AA;
ALIGNMENT:
Query Match 99.6%; Score 1383; Length 364;
Best Local Similarity 100.0%;
Matches 283; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 TSDDDVKKAATVAIVAAYNNGQEINGFKAGETIYDIGEDGTITQKDATAADVEADDFKGL 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 27 TSDDDVKKAATVAIVAAYNNGQEINGFKAGETIYDIGEDGTITQKDATAADVEADDFKGL 86
Qy 62 GLKKVVTNLTKTVNENKQNVDAKVKAAESEIEKLTTKLADTDAALADTDAALDETTNALN 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 87 GLKKVVTNLTKTVNENKQNVDAKVKAAESEIEKLTTKLADTDAALADTDAALDETTNALN 146
Qy 122 KLGENITTFAEETKTNIVKIDEKLEAVADTVDKHAEAFNDIADSLDETNTKADEAVKTAN 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 147 KLGENITTFAEETKTNIVKIDEKLEAVADTVDKHAEAFNDIADSLDETNTKADEAVKTAN 206
Qy 182 EAKQTAEETKQNVDAKVKAAETAAGKAEAAAGTANTAADKAEAVAAKVTDIKADIATNKA 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 207 EAKQTAEETKQNVDAKVKAAETAAGKAEAAAGTANTAADKAEAVAAKVTDIKADIATNKA 266
Qy 242 DIAKNSARIDSLDKNVANLRKETRQGLAEQAALSGLFQPYNVG 284
|||||||||||||||||||||||||||||||||||||||||||
Db 267 DIAKNSARIDSLDKNVANLRKETRQGLAEQAALSGLFQPYNVG 309
Alignment with instantly recited SEQ ID NO:6
ID AZR46705 standard; protein; 255 AA.
AC AZR46705;
XX
DT 16-FEB-2012 (first entry)
XX
DE N. meningitidis strain MC58 fHbp protein (first antigen), SEQ ID 26.
XX
KW Factor H binding protein; antibacterial; antigen; fHbp protein;
KW immune stimulation; immunogenicity; neisseria meningitidis infection;
KW prophylactic to disease; therapeutic; vaccine antibacterial;
KW vaccine, general; BOND_PC; putative lipoprotein precursor;
KW putative lipoprotein; lipoprotein precursor; lipoprotein.
XX
OS Neisseria meningitidis MC58.
XX
CC PN WO2011161653-A1.
CC PD 29-DEC-2011.
CC PF 24-JUN-2011; 2011WO-IB052785.
XX
PR 25-JUN-2010; 2010US-0358816P.
XX
CC PA (NOVS ) NOVARTIS AG.
XX
CC PI Arico BM, Brunelli B, Comanducci M, Pizza M, Savino S;
CC PI Scarselli M;
XX
DR WPI; 2012-A08202/04.
DR PC:NCBI; gi40353455.
XX
CC PT Immunogenic composition useful for treating a disease caused by Neisseria
CC PT meningitidis comprises two different meningococcal factor H binding
CC PT proteins.
XX
CC PS Disclosure; SEQ ID NO 26; 41pp; English.
XX
CC The present invention relates to a novel immunogenic composition
CC (vaccine) comprising two different Meningococcal factor H binding protein
CC (fHbp) antigens. Polypeptides and polynucleotides of the invention are
CC used in the immunogenic composition for treating disease caused by
CC Neisseria meningitidis. The immunogenic composition of the invention
CC useful for raising an immune response against meningococcus. The
CC immunogenic composition can also be used for preventing or treating
CC disease caused by Neisseria meningitidis. The present sequence is a N.
CC meningitidis strain MC58 fHbp antigen (first antigen) used in the
CC composition, of the invention.
CC
CC Revised record issued on 03-FEB-2012 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 255 AA;
ALIGNMENT:
Query Match 100.0%; Score 1294; Length 255;
Best Local Similarity 100.0%;
Matches 255; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CSSGGGGVAADIGAGLADALTAPLDHKDKGLQSLTLDQSVRKNEKLKLAAQGAEKTYGNG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CSSGGGGVAADIGAGLADALTAPLDHKDKGLQSLTLDQSVRKNEKLKLAAQGAEKTYGNG 60
Qy 61 DSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTAFQTEQIQDSEHS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DSLNTGKLKNDKVSRFDFIRQIEVDGQLITLESGEFQVYKQSHSALTAFQTEQIQDSEHS 120
Qy 121 GKMVAKRQFRIGDIAGEHTSFDKLPEGGRATYRGTAFGSDDAGGKLTYTIDFAAKQGNGK 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GKMVAKRQFRIGDIAGEHTSFDKLPEGGRATYRGTAFGSDDAGGKLTYTIDFAAKQGNGK 180
Qy 181 IEHLKSPELNVDLAAADIKPDGKRHAVISGSVLYNQAEKGSYSLGIFGGKAQEVAGSAEV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 IEHLKSPELNVDLAAADIKPDGKRHAVISGSVLYNQAEKGSYSLGIFGGKAQEVAGSAEV 240
Qy 241 KTVNGIRHIGLAAKQ 255
|||||||||||||||
Db 241 KTVNGIRHIGLAAKQ 255
Conclusion
9. No claims allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Peter Paras, can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/Primary Examiner, Art Unit 1645
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