IP Library › Granted Patent US 12,370,247
Granted Patent B2
US 12,370,247 · App. 18/202,842 · Granted Jul 29, 2025

Multivalent pneumococcal vaccines

Inventors: Richard Malley (Beverly, MA); Yingjie Lu (West Roxbury, MA); Fan Zhang (West Roxbury, MA); Teresa J. Broering (Brookline, MA); Shite Sebastian (Shrewsbury, MA); Velupillai Puvanesarajah (Chapel Hill, NC); George R. Siber (New York, NY)
Assignee: Affinivax, Inc.
A61K39/092A61K2039/55505A61K2039/62A61K2039/70
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,370,247
App. No.
18/202,842
Granted
Jul 29, 2025
Kind
B2
Abstract

Technologies for the prevention and/or treatment of pneumococcal infections.

Claims (147)

1. A multivalent vaccine comprising twenty-four or more species of immunogenic complexes, wherein the twenty-four or more species of immunogenic complexes comprise:

a first immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 1, and (b) a fusion protein;

a second immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 2, and (b) a fusion protein;

a third immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 3, and (b) a fusion protein;

a fourth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 4, and (b) a fusion protein;

a fifth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 5, and (b) a fusion protein;

a sixth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 6A, and

(b) a fusion protein;

a seventh immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 6B, and

(b) a fusion protein;

an eighth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 7F, and

(b) a fusion protein;

a ninth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 8, and (b) a fusion protein;

a tenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 9N, and

(b) a fusion protein;

an eleventh immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 9V, and

(b) a fusion protein;

a twelfth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 10A, and

(b) a fusion protein;

a thirteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 11A, and

(b) a fusion protein;

a fourteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 12F, and

(b) a fusion protein;

a fifteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 14, and

(b) a fusion protein;

a sixteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 15B, and

(b) a fusion protein;

a seventeenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 17F, and (b) a fusion protein;

an eighteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 18C, and (b) a fusion protein;

a nineteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 19A, and

(b) a fusion protein;

a twentieth immunogenic complex comprising (a) a biotinylated polysaccharide antigen, comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 19F, and

(b) a fusion protein;

a twenty-first immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 20B, and (b) a fusion protein;

a twenty-second immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 22F, and (b) a fusion protein;

a twenty-third immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 23F and (b) a fusion protein; and

a twenty-fourth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 33F, and (b) a fusion protein;

wherein each fusion protein comprises:

(i) a biotin-binding moiety;

(ii) a first polypeptide antigen comprising an SP1500 polypeptide or an antigenic fragment thereof; and

(iii) a second polypeptide antigen comprising an SP0785 polypeptide or an antigenic fragment thereof;

wherein each fusion protein comprises an amino acid sequence at least 95% identical to SEQ ID NO:6; and

wherein in each species of the immunogenic complexes, the biotinylated polysaccharide antigen is non-covalently associated with the biotin-binding moiety of the fusion protein.

2. The vaccine of claim 1 , wherein the first polypeptide antigen comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO: 5 or an antigenic fragment thereof.

3. The vaccine of claim 2 , wherein the first polypeptide antigen comprises the amino acid sequence of SEQ ID NO: 5.

4. The vaccine of claim 1 , wherein the second polypeptide antigen comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO: 4 or an antigenic fragment thereof.

5. The vaccine of claim 4 , wherein the second polypeptide antigen comprises the amino acid sequence of SEQ ID NO: 4.

6. The vaccine of claim 1 , wherein the biotin-binding moiety is a polypeptide comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO: 2 or a biotin-binding fragment thereof.

7. The vaccine of claim 6 , wherein the biotin-binding moiety is a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.

8. The vaccine of claim 1 , wherein the fusion protein comprises an amino acid sequence at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO: 6.

9. The vaccine of claim 8 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 6.

10. The vaccine of claim 1 , wherein the polysaccharide antigens of the twenty-four or more species of immunogenic complexes are present at stoichiometrically equal ratios, by weight.

11. The vaccine of claim 1 , wherein at least one of the polysaccharide antigens of the twenty-four or more species of immunogenic complexes is present at a stoichiometrically different ratio, by weight, relative to at least one of the other polysaccharide antigens of the twenty-four or more species of immunogenic complexes.

12. The vaccine of claim 1 , wherein the polysaccharide antigens of the twenty-four or more species of immunogenic complexes are present at stoichiometrically different ratios, by weight.

13. A pharmaceutical composition comprising the vaccine of claim 1 , and a pharmaceutically acceptable carrier.

14. The pharmaceutical composition of claim 13 , further comprising one or more adjuvants.

15. The pharmaceutical composition of claim 14 , wherein the one or more adjuvants is or comprises a co-stimulation factor.

16. The pharmaceutical composition of claim 14 , wherein the one or more adjuvants are selected from the group consisting of aluminum phosphate, aluminum hydroxide, and phosphated aluminum hydroxide.

17. The pharmaceutical composition of claim 16 , wherein the one or more adjuvants is or comprises aluminum phosphate.

18. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition is formulated for injection.

19. A method of making a multivalent vaccine, the method comprising a step of: mixing twenty-four or more species of immunogenic complexes in a single formulation,

wherein the twenty-four or more species of immunogenic complexes comprise:

a first immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 1, and (b) a fusion protein;

a second immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 2, and (b) a fusion protein;

a third immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 3, and (b) a fusion protein;

a fourth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 4, and (b) a fusion protein;

a fifth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 5, and (b) a fusion protein;

a sixth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 6A, and

(b) a fusion protein;

a seventh immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 6B, and

(b) a fusion protein;

an eighth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 7F, and

(b) a fusion protein;

a ninth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 8, and (b) a fusion protein;

a tenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 9N, and

(b) a fusion protein;

an eleventh immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 9V, and

(b) a fusion protein;

a twelfth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 10A, and

(b) a fusion protein;

a thirteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 11A, and

(b) a fusion protein;

a fourteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 12F, and

(b) a fusion protein;

a fifteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 14, and

(b) a fusion protein;

a sixteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 15B, and

(b) a fusion protein;

a seventeenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 17F, and (b) a fusion protein;

an eighteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 18C, and (b) a fusion protein;

a nineteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 19A, and

(b) a fusion protein;

a twentieth immunogenic complex comprising (a) a biotinylated polysaccharide antigen, comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 19F, and

(b) a fusion protein;

a twenty-first immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 20B, and (b) a fusion protein;

a twenty-second immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 22F, and (b) a fusion protein;

a twenty-third immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 23F and (b) a fusion protein; and

a twenty-fourth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 33F, and (b) a fusion protein;

wherein each fusion protein comprises:

(i) a biotin-binding moiety;

(ii) a first polypeptide antigen comprising an SP1500 polypeptide or an antigenic fragment thereof; and

(iii) a second polypeptide antigen comprising an SP0785 polypeptide or an antigenic fragment thereof;

wherein each fusion protein comprises an amino acid sequence at least 95% identical to SEQ ID NO:6; and

wherein in each species of the immunogenic complexes, the biotinylated polysaccharide antigen is non-covalently associated with the biotin-binding moiety of the fusion protein.

20. A method of immunizing a subject against Streptococcus pneumoniae infection and/or colonization comprising administering to the subject a multivalent vaccine comprising twenty-four or more species of immunogenic complexes, wherein the twenty-four or more species of immunogenic complexes comprise:

a first immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 1, and (b) a fusion protein;

a second immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 2, and (b) a fusion protein;

a third immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 3, and (b) a fusion protein;

a fourth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 4, and (b) a fusion protein;

a fifth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 5, and (b) a fusion protein;

a sixth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 6A, and

(b) a fusion protein;

a seventh immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 6B, and

(b) a fusion protein;

an eighth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 7F, and

(b) a fusion protein;

a ninth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 8, and (b) a fusion protein;

a tenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 9N, and

(b) a fusion protein;

an eleventh immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 9V, and

(b) a fusion protein;

a twelfth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 10A, and

(b) a fusion protein;

a thirteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 11A, and

(b) a fusion protein;

a fourteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 12F, and

(b) a fusion protein;

a fifteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 14, and

(b) a fusion protein;

a sixteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 15B, and

(b) a fusion protein;

a seventeenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 17F, and (b) a fusion protein;

an eighteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 18C, and (b) a fusion protein;

a nineteenth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 19A, and

(b) a fusion protein;

a twentieth immunogenic complex comprising (a) a biotinylated polysaccharide antigen, comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 19F, and

(b) a fusion protein;

a twenty-first immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 20B, and (b) a fusion protein;

a twenty-second immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 22F, and (b) a fusion protein;

a twenty-third immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 23F and (b) a fusion protein; and

a twenty-fourth immunogenic complex comprising (a) a biotinylated polysaccharide antigen comprising biotin and a polysaccharide antigen of Streptococcus pneumoniae serotype 33F, and (b) a fusion protein;

wherein each fusion protein comprises:

(i) a biotin-binding moiety;

(ii) a first polypeptide antigen comprising an SP1500 polypeptide or an antigenic fragment thereof; and

(iii) a second polypeptide antigen comprising an SP0785 polypeptide or an antigenic fragment thereof;

wherein each fusion protein comprises an amino acid sequence at least 95% identical to SEQ ID NO:6; and

wherein in each species of the immunogenic complexes, the biotinylated polysaccharide antigen is non-covalently associated with the biotin-binding moiety of the fusion protein.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 28, 2023
From: MALLEY, RICHARD; LU, YINGJIE; ZHANG, FAN; BROERING, TERESA J.; SEBASTIAN, SHITE; PUVANESARAJAH, VELUPILLAI; SIBER, GEORGE R.
To: AFFINIVAX, INC.
Reel/Frame 064728/0001 →
Continuity (4)
Continuation 17237168 · Apr 22, 2021
Division 16569579 · Sep 12, 2019
Provisional Application 62730471 · Sep 12, 2018
Related Publication 20230390375A1 · Dec 7, 2023
References Cited (225)
US 6287568B1 · Wang et al. · 2001 [cited by applicant]
US 7217791B2 · Chen et al. · 2007 [cited by applicant]
US 7585669B2 · Chen et al. · 2009 [cited by applicant]
US 9499593B2 · Malley et al. · 2016 [cited by applicant]
US 10017548B2 · Malley et al. · 2018 [cited by applicant]
US 11013793B2 · Malley et al. · 2021 [cited by applicant]
US 11576958B2 · Malley et al. · 2023 [cited by applicant]
US 11701416B2 · Malley et al. · 2023 [cited by applicant]
US 20020032323A1 · Kunsch et al. · 2002 [cited by applicant]
US 20050002948A1 · Ryall · 2005 [cited by applicant]
US 20050226899A1 · Castiglioni et al. · 2005 [cited by applicant]
US 20060251675A1 · Hagen · 2006 [cited by applicant]
US 20070082005A1 · Doucette-Stamm et al. · 2007 [cited by applicant]
US 20070128183A1 · Meinke et al. · 2007 [cited by applicant]
US 20070184443A1 · Covacci · 2007 [cited by applicant]
US 20080032340A1 · Ghosh et al. · 2008 [cited by applicant]
US 20080112964A1 · Kirkham et al. · 2008 [cited by applicant]
US 20080160045A1 · Contorni et al. · 2008 [cited by applicant]
US 20090054251A1 · O'Connor et al. · 2009 [cited by applicant]
US 20090068288A1 · Kruger · 2009 [cited by applicant]
US 20090148894A1 · Broedel et al. · 2009 [cited by applicant]
US 20090148897A1 · Dai · 2009 [cited by applicant]
US 20090285846A1 · Tweten · 2009 [cited by applicant]
US 20100003266A1 · Simon · 2010 [cited by applicant]
US 20100020945A1 · Li et al. · 2010 [cited by applicant]
US 20100022401A1 · Nordlund et al. · 2010 [cited by applicant]
US 20100166802A1 · Caplan et al. · 2010 [cited by applicant]
US 20100209450A1 · Biemans et al. · 2010 [cited by applicant]
US 20100330112A1 · Long et al. · 2010 [cited by applicant]
US 20110020386A1 · Gierahn et al. · 2011 [cited by applicant]
US 20110065660A1 · Baron et al. · 2011 [cited by applicant]
US 20110159040A1 · Malley et al. · 2011 [cited by applicant]
US 20110293664A1 · Cohane et al. · 2011 [cited by applicant]
US 20120135025A1 · Flechtner et al. · 2012 [cited by applicant]
US 20120189649A1 · Gierahn et al. · 2012 [cited by applicant]
US 20120251577A1 · Malley et al. · 2012 [cited by applicant]
US 20130115230A1 · Simon · 2013 [cited by applicant]
US 20130121958A1 · Leclerc et al. · 2013 [cited by applicant]
US 20140154286A1 · Malley et al. · 2014 [cited by applicant]
US 20140154287A1 · Malley et al. · 2014 [cited by applicant]
US 20150374811A1 · Malley et al. · 2015 [cited by applicant]
US 20160090404A1 · Malley et al. · 2016 [cited by applicant]
US 20170021006A1 · Watson et al. · 2017 [cited by applicant]
US 20190119335A1 · Malley et al. · 2019 [cited by applicant]
US 20200087361A1 · Malley et al. · 2020 [cited by applicant]
US 20200222522A1 · Malley et al. · 2020 [cited by applicant]
US 20200407404A1 · Malley et al. · 2020 [cited by applicant]
US 20210346487A1 · Malley et al. · 2021 [cited by applicant]
EA 200801374A1 · 2008 [cited by applicant]
EA 200801935A1 · 2009 [cited by applicant]
EP 0497524A2 · 1992 [cited by applicant]
EP 1838345A2 · 2007 [cited by applicant]
JP H11502820A · 1999 [cited by applicant]
JP 2001505415A · 2001 [cited by applicant]
JP 2002504096A · 2002 [cited by applicant]
JP 2002521058A · 2002 [cited by applicant]
JP 2007504237A · 2007 [cited by applicant]
JP 2008509682A · 2008 [cited by applicant]
JP 2010517532A · 2010 [cited by applicant]
JP 2014514363A · 2014 [cited by applicant]
JP 2014517835A · 2014 [cited by applicant]
JP 2016509011A · 2016 [cited by applicant]
KR 20080090411A · 2008 [cited by applicant]
RU 2164943C2 · 2001 [cited by applicant]
RU 2006117425A · 2007 [cited by applicant]
RU 2378008C2 · 2010 [cited by applicant]
RU 2407749C2 · 2010 [cited by applicant]
RU 2524436C2 · 2014 [cited by applicant]
WO WO9011087A1 · 1990 [cited by applicant]
WO WO1995021195A1 · 1995 [cited by applicant]
WO WO1996029094A1 · 1996 [cited by applicant]
WO WO1998018930A2 · 1998 [cited by applicant]
WO WO9847530A2 · 1998 [cited by applicant]
WO WO9903884A2 · 1999 [cited by applicant]
WO WO0006737A2 · 2000 [cited by applicant]
WO WO2000006738A2 · 2000 [cited by applicant]
WO WO0140472A2 · 2001 [cited by applicant]
WO WO02077021A2 · 2002 [cited by applicant]
WO WO2003044185A2 · 2003 [cited by applicant]
WO WO2003094960A2 · 2003 [cited by applicant]
WO WO2004092209A2 · 2004 [cited by applicant]
WO WO2005037190A2 · 2005 [cited by applicant]
WO WO2005039501A2 · 2005 [cited by applicant]
WO WO2006017929A1 · 2006 [cited by applicant]
WO WO2006067632A2 · 2006 [cited by applicant]
WO WO2006084467A1 · 2006 [cited by applicant]
WO WO2007026249A2 · 2007 [cited by applicant]
WO WO2007067681A2 · 2007 [cited by applicant]
WO WO2007068907A2 · 2007 [cited by applicant]
WO WO2007071711A2 · 2007 [cited by applicant]
WO WO2007081583A2 · 2007 [cited by applicant]
WO WO2007116028A2 · 2007 [cited by applicant]
WO WO2007150020A1 · 2007 [cited by applicant]
WO WO2008094986A2 · 2008 [cited by applicant]
WO WO2008119358A2 · 2008 [cited by applicant]
WO WO2008152448A2 · 2008 [cited by applicant]
WO WO2009016515A2 · 2009 [cited by applicant]
WO WO2009021548A1 · 2009 [cited by applicant]
WO WO2009029831A1 · 2009 [cited by applicant]
WO WO2009143413A1 · 2009 [cited by applicant]
WO WO2010053559A1 · 2010 [cited by applicant]
WO WO2010071986A1 · 2010 [cited by applicant]
WO WO2010080484A1 · 2010 [cited by applicant]
WO WO2010081875A1 · 2010 [cited by applicant]
WO WO2011008548A1 · 2011 [cited by applicant]
WO WO2011137354A2 · 2011 [cited by applicant]
WO WO2012155007A1 · 2012 [cited by applicant]
WO WO2012155053A1 · 2012 [cited by applicant]
WO WO2014018904A1 · 2014 [cited by applicant]
WO WO2014124228A1 · 2014 [cited by applicant]
WO WO2017013548A1 · 2017 [cited by applicant]
WO WO2018183475A1 · 2018 [cited by applicant]
WO WO2020056127A1 · 2020 [cited by applicant]
WO WO2020056202A1 · 2020 [cited by applicant]
Skinner, J. M. et al., “Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15- CRM197) in an infant-rhesus monkey immunogenicity model”, Vaccine, 29(48): 8870-6; 2011. [cited by applicant]
“Centers for Disease Control and Prevention. ”“Preventing pneumococcal disease among infants and young children.” “Morbidity and Mortality Weekly Report. 49: 1-55 (2000)”. [cited by applicant]
Ahmad, A. et al., Sequential release of antigens from chloroform-treated [cited by applicant]
Anttila, M. et al., Avidity of IgG for [cited by applicant]
Avci, F.Y. et al., A mechanism for glycoconjugate vaccine activation of the adaptive immune system and its implications or vaccine design, Nat. Med., 17(12): 1602-1609 (2011). [cited by applicant]
Basset, A et al., Antibody-independent, CD4+ T-Cell-Dependent protection against pneumococcal colonization elicited by intranasal immunization with purified pneumococcal proteins, Infection and Immunity, 75(11):5460-546… [cited by applicant]
Beghetto, E. et al., Discovery of novel [cited by applicant]
Berry, M. A. et al., Effect of Defined Point Mutations in Pneumolysin Gene on the Virulence of [cited by applicant]
Boslego et al., “Gonorrhea Vaccines” Vaccine and Immunotherapy Ch. 17 211 (1991). [cited by applicant]
Bowie, J. U. et al., Deciphering the message in protein sequences: tolerance to amino acid substitutions, Science, 257(4948):1306-1310 (1990). [cited by applicant]
Caierao, J. et al., Characteristics of serogroup 20 S.pneumoniae isolates from Brazil, BMC Infectious Diseases, 16:418 (2016). [cited by applicant]
Centers for Disease Control and Prevention. “Prevention of pneumococcal disease among infants and children—use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine.” Morbidity an… [cited by applicant]
Chichili, G.R. et al., Phase 1/2 study of a novel 24-valent pneumococcal vaccine in healthy adults aged 18 to 64 years and in older adults aged 65 to 85 years, Vaccine, 40(31):4190-4198, (2022). [cited by applicant]
Colino, J. et al., Noncovalent association of protein and capsular polysaccharide on bacteria-sized latex beads as a model for polysaccharide-specific humoral immunity to intact Gram-positive extracellular bacteria, J. … [cited by applicant]
Colino, J. et al., Parameters Underlying Distinct T Cell-Dependent Polysaccharide-Specific IgG Responses to an Intact Gram-Positive Bacterium versus a Soluble Conjugate Vaccine, The Journal of Immunology, 1552-1559 (200… [cited by applicant]
Cortajarena, A.L., et al., A receptor-binding region in [cited by applicant]
Dagan, R. et al., Glycoconjugate vaccines and immune interference: A review, Vaccine, 28(34): 5513-5523 (2010). [cited by applicant]
Daniels, C. C. et al., The Proline-Rich Region of Pneumococcal Surface Proteins A and C Contains Surface-Accessible Epitopes Common to All Pneumococci and Elicits Antibody-Mediated Protection against Sepsis, Infection a… [cited by applicant]
Database, Online GenBank: ATJ19904.1, retrieved on Aug. 22, 2023. [cited by applicant]
Database, Online GenBank: ATJ19907.1, retrieved on Aug. 8, 2023. [cited by applicant]
Database, UniProt KB/TrEMBL, B3Q265_RHIE6, retrieved Jan. 3, 2021. [cited by applicant]
Database, UniProt KB/TrEMBL, F2AA21_RHIET, retrieved Jan. 4, 2021. [cited by applicant]
Database, UniProt KB/TrEMBL, Q8KKW2_RHIEC, retrieved Jan. 4, 2021. [cited by applicant]
Douce, G. et al., Genetically detoxified mutants of heat-labile toxin from [cited by applicant]
Douce, G et al., Mutants of [cited by applicant]
Elgert, K. D., Immunology Understanding the Immune System, John Wiley & Sons, Inc. Hoboken, New Jersey, p. 111 (2009). [cited by applicant]
Ellis, New Technologies for making vaccines, Vaccine Ch. 29, 568-574 (1988). [cited by applicant]
Evans, J. T. et al., Enhancement of antigen-specific immunity via the TLR4 ligands MPL adjuvant and Ribi.529, Expert Rev Vaccines, 2(2):219-229 (2003). [cited by applicant]
Fauvart, M. et al., Genome Sequence of Rhizobium etli CNPAF512, a Nitrogen-Fixing Symbiont Isolated from Bean Root Nodules in Brazil, Journal of Bacteriology, 193(12): 3158-3159 (2011). [cited by applicant]
Ferreira, D. M. et al., DNA vaccines based on genetically detoxified derivatives of pneumolysin fail to protect mice against challenge with [cited by applicant]
Gaj, T. et al., The AviD-tag, a NeutrAvidin/avidin specific peptide affinity tag for the immobilization and purification of recombinant proteins, Protein Expr. Purif., 56(1):54-61 (2007). [cited by applicant]
Giuliani, M. M. et al., Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of [cited by applicant]
González, V. et al., The mosaic structure of the symbiotic plasmid of Rhizobium etli CFN42 and its relation to other symbiotic genome compartments, Genome Biol., 4(6): R36 (2003). [cited by applicant]
Greenspan, N. S. and Cera, E. D., Defining epitopes: It's not easy as it seems, Nature Biotechnology, 17:936-937 (1999). [cited by applicant]
Gruber, M.F. et al., Licensing of pneumococcal conjugate vaccines for children and adults: Regulatory perspective from the European Medicines Agency and the U.S. Food and Drug Administration, Pneumococcal Vaccines: The … [cited by applicant]
Grun, C. H. et al., One-step biotinylation procedure for carbohydrates to study carbohydrate-protein interactions, Anal. Biochem., 354(1):54-63 (2006). [cited by applicant]
Helppolainen, S. H. et al., Bradavidin II from Bradyrhizobium japonicum: a new avidin-like biotin-binding protein, Biochim. Biophys. Acta., 1784(7-8):1002-10 (2008). [cited by applicant]
Helppolainen, S.H. et al., Rhizavidin from Rhizobium etli: the first natural dimer in the avidin protein family, Biochem J., 405(3): 397-405 (2007). [cited by applicant]
Hermanson, G. T., Bioconjugate Techniques, Elsevier Science, ProQuest Ebook Central, http://ebookcentral.proquest.com/lib.USPTO-ebooks/detail.action?docID=307203, created from uspto-ebooks on Sep. 6, 2017, 570-592 (1996… [cited by applicant]
Holliger, P et al., “Diabodies”: small bivalent and bi specific antibody fragments, Proc. Natl. Acad, Sci, USA, 90:6444-6448 (1993). [cited by applicant]
Hsu, T-L. et al., Profiling Carbohydrate-Receptor Interaction with Recombinant Innate Immunity Receptor-Fc Fusion Proteins, J. Biol. Chem., 284(50): 34479-34489 (2009). [cited by applicant]
Huang, H. et al., Robust stimulation of humoral and cellular immune responses following vaccination with antigen-loaded beta-glucan particles, MBio, 1(3):e00164-10 (2010). [cited by applicant]
Hytonen, V.P. et al., Efficient production of active chicken avidin using a bacterial signal peptide in [cited by applicant]
Insel, R. et al., Response to oligosaccharide-protein conjugate vaccine against Hemophilus Influenzae b in two patients with lgG2 deficiency unresponsive to capsular polysaccharide vaccine, N. Engl J. Med., 315:8, p. 49… [cited by applicant]
International Search Report for PCT/2019/050907 (Multivalent Pneumococcal Vaccines, filed Sep. 12, 2019), issued by ISA/US, 5 pages (mailed Feb. 2, 2020). [cited by applicant]
International Search Report for PCT/US19/50800 (Pneumococcal Fusion Protein Vaccines, filed Sep. 12, 2019), issued by ISA/US, 4 pages (mailed Dec. 31, 2019). [cited by applicant]
International Search Report for PCT/US2012/037412 (Multiple Antigen Presenting Immunogenic Composition, and Methods and Uses Thereof, filed May 11, 2012), issued by ISA/FIPS, 3 pages (mailed Aug. 23, 2012). [cited by applicant]
International Search Report for PCT/US2012/037541 (Modified Biotin-Binding Protein, Fusion Proteins Thereof and Applications, filed May 11, 2012), issued by ISA/FIPS, 4 pages (mailed Aug. 30, 2012). [cited by applicant]
International Search Report for PCT/US2014/015254 (Protein Antigens That Provide Protection Against Pneumococcal Colonization And/Or Disease, filed Feb. 7, 2014), issued by ISA/US, 4 pages (mailed May 5, 2014). [cited by applicant]
International Search Report for PCT/US2018/24810 (A Multiple Antigen Presenting System (Maps)-Based Staphylococcus Aureus Vaccine, Immunogenic Composition, and Uses Thereof, filed Mar. 28, 2018), issued by ISA/US, 6 pag… [cited by applicant]
Ishizaka, S.T. and Hawkins, L.D., E6020: a synthetic Toll-like receptor 4 agonist as a vaccine adjuvant, Expert Rev. Vaccines, 6(5):773-784 (2007). [cited by applicant]
Izard, J. W. and Kendall, D. A., Signal peptides: exquisitely designed transport promoters, Mol. Microbiol. 13(5):765-73 (1994). [cited by applicant]
Jin, Z. et al., Conjugates of group A and W135 capsular polysaccharides of neisseria meningitidis bound to recombinant [cited by applicant]
Kehoe, M. et al., Cloning, Expression, and Mapping of the [cited by applicant]
Kim, K. H et al., Efficiency of a Pneumococcal Opsonophagocytic Killing Assay Improved by Multiplexing and by Coloring Colonies, Clin. Diagn. Lab. Immunol., 10(4):616-621 (2003). [cited by applicant]
Kojima, K. et al., Quantitation of lgG subclass antibodies to pneumococcal capsular polysaccharides by ELISA, using Pneumovax-specific antibodies as a reference, Tohoku J. Exp. Med., 161(3):209-215 (1990). [cited by applicant]
Koskela, M. and Leinonen, M., Comparison of ELISA and RIA for measurement of pneumococcal antibodies before and after vaccination with 14-valent pneumococcal capsular polysaccharide vaccine, J. Clin. Pathol., 34(1):93-9… [cited by applicant]
Laine, C. et al., Age-specific immunoglobulin G (IgG) and IgA to pneumococcal protein antigens in a population in coastal Kenya, Infection and Immunity, 72(6):3331-3335 (2004). [cited by applicant]
Lees, A. et al., Enhanced immunogenicity of protein-dextran conjugates: I. Rapid stimulation of enhanced antibody responses to poorly immunogenic molecules, Vaccine, 12(13): 1160-1166 (1994). [cited by applicant]
Ling, E. et al., Glycolytic enzymes associated with the cell surface of [cited by applicant]
Lu, Y. J et al., A Bivalent Vaccine to Protect against [cited by applicant]
Lu, Y. J et al., Protection against Pneumococcal Colonization and Fatal Pneumonia by a Trivalent Conjugate of a Fusion Protein with the Cell Wall Polysaccharide, Infection and Immunity, 77(5):2076-2083 (2009). [cited by applicant]
Lu, Y. J. et al., Interleukin-17A Mediates Acquired Immunity to Pneumococcal Colonization, PLOS Pathogens, 4(9):1-11 (2008). [cited by applicant]
Malley, R. et al., Antibody and cell-mediated immunity to [cited by applicant]
Malley, R. et al., CD4+ T Cells Mediate Antibody-Independent Acquired Immunity to Pneumococcal Colonization, PNAS, 102(13):4848-4853 (2005). [cited by applicant]
Malley, R. et al., Intranasal Immunization with Killed Unencapsulated Whole Cells Prevents Colonization and Invasive Disease by Capsulated Pneumococci, Infection and Immunity, 69(8):4870-4873 (2001). [cited by applicant]
Malley, R. et al., Multiserotype Protection of Mice Against Pneumococcal Colonization of the Nasopharynx and Middle 3 Ear by Killed Nonencapsulated Cells Given Intranasally with a Nontoxic Adjuvanl, Infection and Immuni… [cited by applicant]
Martinez, J. E. et al., A flow cytometric opsonophagocytic assay for measurement of functional antibodies elicited after vaccination with the 23-valent pneumococcal polysaccharide vaccine, Clin. Diagn. Lab Immunol., 6(4… [cited by applicant]
Moffitt, K. L. et al., Identification of Protective Pneumococcal Th17 Antigens from the Soluble Fraction of a Killed Whole Cell Vaccine, PLoS ONE 7(8):e43445 (2012). [cited by applicant]
Moffitt, K. L. et al., TH17-Based vaccine design for prevention of [cited by applicant]
Munro, C. S. et al., Assessment of biological activity of immunoglobulin preparations by using opsonized micro-organisms to stimulate neutrophil chemiluminescence, Clin. Exp. Immunol., 61(1):183-188 (1985). [cited by applicant]
Nordlund, H. R. et al., Tetravalent single-chain avidin: from subunits to protein domains via circularly permuted avidins, Biochem. J., 392(Pt 3): 485-491 (2005). [cited by applicant]
Nuorti, J. P. and Whitney, C. G., Prevention of pneumococcal disease among infants and children—use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine, Morbidity and Mortality … [cited by applicant]
Ojo-Amaize, E. A. et al., A rapid and sensitive chemiluminescence assay for evaluation of functional opsonic activity of Haemophilus influenzae type b-specific antibodies, Clin. Diagn. Lab. Immunol., 2(3):286-290 (1995). [cited by applicant]
O'Reilly, M. et al., Inactivation of the alpha-haemolysin gene of [cited by applicant]
Paton, P C. et al., Purification and immunogenicity of genetically obtained pneumolysin toxoids and their conjugation to [cited by applicant]
Pneumovax® 23 (prescribing information). Whitehouse Station, NJ: Merck & Co.; May 2015. [cited by applicant]
Poljak, R. J., Production and structure of diabodies, Structure. 2(12):1121-1123 (1994). [cited by applicant]
Pollabauer, E. M. et al., The influence of carrier protein on the immunogenicity of simultaneously administered conjugate vaccines in infants, Vaccine, 27(11): 1674-1679 (2009). [cited by applicant]
Portnoi, M. et al., The vaccine potential of [cited by applicant]
Prevnar 13® (prescribing information). New York, NY: Pfizer; Aug. 2017. [cited by applicant]
Richter, S. S et al., Changes in pneumococcal serotypes and antimicrobial resistance after introduction of the 13 valent conjugate vaccine in the United States, Antimicrob Agents Chemother., 58:6484-6489 (2014). [cited by applicant]
Romero-Steiner, S. et al., Avidity determinations for Haemophilus influenzae Type b anti-polyribosylribitol phosphate antibodies, Clin. Diagn. Lab. Immunol., 12(9):1029-1035 (2005). [cited by applicant]
Romero-Steiner, S. et al., Standardization of an opsonophagocytic assay for the measurement of functional antibody activity against [cited by applicant]
Rosenberg, I.M., Protein Analysis and Purification, Springer Science + Business Media New York, 153-182 (1996). [cited by applicant]
Saeland, E. et al., Pneumococcal pneumonia and bacteremia model in mice for the analysis of protective antibodies, Microb. Pathog., 29(2):81-91 (2000). [cited by applicant]
Sanabria-Valentin, Dissertation, Department of Basic Medical Sciences, NYU, p. 8-9 describing the general structure of LPS (2008). [cited by applicant]
Sano, T et al., Methods in Enzymology, Elsevier, 326: 305-307 (2000). [cited by applicant]
Saunders, F. K. et al., Pneumolysin, the thiol- activated toxin of [cited by applicant]
Scott, D. et al., Immunogenicity of biotinylated hapten-avidin complexes, Mol. Immunol., 21(11):1055-1060 (1984). [cited by applicant]
Sen, G. et al., In vivo humoral immune responses to isolated Pneumococcal polysaccharides are dependent on the presence of associated TLR ligands, The Journal of Immunology, 175(5):3084-3091 (2005). [cited by applicant]
Singh, M. and Indresh S., Advances in vaccine adjuvants for infectious diseases, Current HIV research 1(3):309-320 (2003). [cited by applicant]
Skolnick, J. and Fetrow, J. S., From genes to protein structure and function: novel applications of computational approaches in the genomic era, Trends in Biotechnology, 18:34-39 (2000). [cited by applicant]
Stack, A. M. et al., Minimum protective serum concentrations of pneumococcal anti-capsular antibodies in infant rats, J. Infect. Dis., 177(4):986-990 (1998). [cited by applicant]
Takakura, Y. et al., Tamavidin, a versatile affinity tag for protein purification and immobilization, J. Biotechnol., 145(4): 317-322 (2010). [cited by applicant]
Thermo Scientific Avidin-Biotin Technical Handbook, 2009, p. 16-17. Found on the Internet on May 5, 2016 at: https://www.thermofisher.com/content/dam/LifeTech/Images/integration/1601675_AvBi_HB_INTL.pdf. [cited by applicant]
Trzcinski, K. et al., Antibodies to Conserved Pneumococcal Antigens Correlate with, but Are Not Required for, 5 Protection Against Pneumococcal Colonization Induced by Prior Exposure in a Mouse Model, Infection and Immu… [cited by applicant]
Vickerman, M. M. et al., Genome-wide transcriptional changes in [cited by applicant]
Wardenburg, J. and Schneewind, O., Vaccine protection against [cited by applicant]
Williams et al., Innate Imprinting by the Modified Heat-Labile Toxin of [cited by applicant]
Wizeman et al., Use of a while Genome Approach to Identify Vaccine Molecules Affording Protection against [cited by applicant]
Written Opinion for PCT/2019/050907 (Multivalent Pneumococcal Vaccines, filed Sep. 12, 2019), issued by ISA/US, 6 pages (mailed Feb. 2, 2020). [cited by applicant]
Written Opinion for PCT/US19/50800 (Pneumococcal Fusion Protein Vaccines, filed Sep. 12, 2019), issued by ISA/US, 8 pages (mailed Dec. 31, 2019). [cited by applicant]
Written Opinion for PCT/US2012/037412 (Multiple Antigen Presenting Immunogenic Composition, and Methods and Uses Thereof, filed May 11, 2012), issued by ISA/FIPS, 4 pages (mailed Aug. 23, 2012). [cited by applicant]
Written Opinion for PCT/US2012/037541 (Modified Biotin-Binding Protein, Fusion Proteins Thereof and Applications, filed May 11, 2012), issued by ISA/FIPS, 3 pages (mailed Aug. 30, 2012). [cited by applicant]
Written Opinion for PCT/US2014/015254 (Protein Antigens That Provide Protection Against Pneumococcal Colonization And/Or Disease, filed Feb. 7, 2014), issued by ISA/US, 5 pages (mailed May 5, 2014). [cited by applicant]
Written Opinion for PCT/US2018/24810 (A Multiple Antigen Presenting System (Maps)-Based Staphylococcus Aureus Vaccine, Immunogenic Composition, and Uses Thereof, filed Mar. 28, 2018), issued by ISA/US, 9 pages (mailed A… [cited by applicant]
Wu, W. et al., Th17-stimulating protein vaccines confer protection against Pseudomonas aeruginosa pneumonia, Am. J. Respir. Grit. Care Med., 186(5):420-427 (2012). [cited by applicant]
Zhang, F. et al., Design and evaluation of multiple antigen presenting system (MAPS)-based pneumococcal vaccine to prevent invasive disease and carriage, poster presented at the 10th International Symposium on Pneumococ… [cited by applicant]
Zhang, F. et al., Multiple antigen-presenting system (MAPS) to induce comprehensive B- and T-cell immunity, Proc. Natl. Acad. Sci., 110(33):13564-13569 (2013). [cited by applicant]
Zhang, F. et al., Protection against [cited by applicant]