Saccharide-polypeptide conjugate compositions and methods of use thereof

Abstract

Saccharide-polypeptide conjugates, compositions containing these, methods of making and using the conjugates and compositions, and kits containing these, are disclosed.

1 - 295 . (canceled) 
     
     
         296 . A pharmaceutical composition comprising at least 2 immunogenic saccharide-polypeptide conjugates each comprising individually a capsular polysaccharide, fragment thereof, or combination thereof, conjugated to a polypeptide, wherein the capsular polysaccharide, fragment thereof, or combination thereof is from a unique  Streptococcus pneumoniae  serotype group, wherein a first serotype is selected from the group consisting of 6C, 15A, 16F, 20B, 24F, 31, and 34 and at least one additional serotype is selected from the group consisting of 1, 2, 3, 4, 5, 6A, 6B, 6C, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 9N, 10A, 11A, 12F, 15A, 15B, 15C, 16F, 17F, 20A, 22F, 23A, 23B, 24F, 31, 33F, 34, 35B, and 38, wherein the at least one additional serotype is not the first serotype. 
     
     
         297 . The pharmaceutical composition of  claim 296 , wherein the first serotype is 20B. 
     
     
         298 . The pharmaceutical composition of  claim 296 , wherein the first serotype is 6C. 
     
     
         299 . The pharmaceutical composition of  claim 296 , wherein the first serotype is 15A. 
     
     
         300 . The pharmaceutical composition of  claim 296 , wherein the first serotype is 16F. 
     
     
         301 . The pharmaceutical composition of  claim 296 , wherein at least one polypeptide comprises a mixture of polypeptides. 
     
     
         302 . The pharmaceutical composition of  claim 296 , wherein at least one polypeptide comprises CRM 197 , tetanus toxoid, a diphtheria toxoid, cholera toxoid, pertussis toxoid, inactivated or mutant pneumococcal pneumolysin, pneumococcal surface protein A, pneumococcal adhesion protein A, pneumococcal lipoprotein PsaA, C5a peptidase group A or group B  Streptococcus , a non-typable  H. influenzae  P4 protein, a non-typable  H. influenzae  P6 protein,  M. catarrhalis  uspA, keyhole limpet haemocyanin (KLH), OMPC from  N. meningitidis , a purified protein derivative of tuberculin (PPD), protein D from  H. influenzae , PspA, any fragment thereof, or any combination thereof. 
     
     
         303 . The pharmaceutical composition of  claim 296 , further comprising an adjuvant; a chelating agent; a surfactant; an emulsifier; a buffering agent; a preservative; a salt; an anti-fungal compound; or a combination thereof. 
     
     
         304 . The pharmaceutical composition of  claim 296 , wherein the pharmaceutical composition is in the form of an intramuscularly injectable composition, intradermally injectable composition, subcutaneously injectable composition, or an intranasally administrable composition. 
     
     
         305 . The pharmaceutical composition of  claim 296 , wherein at least one of the immunogenic saccharide-polypeptide conjugates elicits an opsonophagocytic response. 
     
     
         306 . The pharmaceutical composition of  claim 296 , wherein the immunogenic saccharide-polypeptide conjugates are collectively present in an amount of at least 0.001%, by weight, based on the weight of the pharmaceutical composition. 
     
     
         307 . The pharmaceutical composition of  claim 296 , wherein the immunogenic saccharide-polypeptide conjugates comprise: (i) the capsular polysaccharide at least partially embedded in the polypeptide, (ii) the capsular polysaccharide chemically cross-linked to the polypeptide, and/or (iii) the capsular polysaccharide at least partially chemically cross-linked to the polypeptide. 
     
     
         308 . The pharmaceutical composition of  claim 296 , wherein a toxin activity of at least one of the polypeptides is at least partly mitigated. 
     
     
         309 . The pharmaceutical composition of  claim 296 , wherein each of the immunogenic saccharide-polypeptide conjugates is present in an amount of at least 0.001%, by weight, based on the weight of the pharmaceutical composition. 
     
     
         310 . A method comprising administering to a subject a first composition, wherein the first composition comprises the pharmaceutical composition of  claim 296 . 
     
     
         311 . The method of  claim 310 , wherein the first composition is administered intramuscularly. 
     
     
         312 . The method of  claim 310 , wherein the administering to the subject the first composition occurs at least about four weeks before or at least about four weeks after an administration of a second composition comprising an immunogenic saccharide-polypeptide conjugate. 
     
     
         313 . The method of  claim 312 , wherein the second composition comprises an immunogenic saccharide-polypeptide conjugate comprising a capsular polysaccharide from a serotype of  Streptococcus pneumoniae  conjugated to a second polypeptide. 
     
     
         314 . The method of  claim 310 , wherein the subject is a human. 
     
     
         315 . A method of making a composition comprising: contacting the plurality of immunogenic saccharide-polypeptide conjugates of  claim 296  with an excipient, an adjuvant, or any combination thereof.