US2011305727A1PendingUtilityA1

Rsv f protein compositions and methods for making same

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Assignee: SWANSON KURTPriority: Jul 15, 2009Filed: Jul 15, 2010Published: Dec 15, 2011
Est. expiryJul 15, 2029(~3 yrs left)· nominal 20-yr term from priority
Inventors:Kurt SwansonPhilip Dormitzer
A61P 37/04A61P 31/14A61P 11/00C07K 16/11A61K 2039/53C07K 2319/21C12N 2760/18534C07K 14/005C07K 2317/76A61K 2039/55505A61K 2039/5252C12N 2760/18522A61K 39/155A61K 2039/5256A61K 2039/55566A61K 2039/55572A61K 2039/5258C07K 2319/73C07K 2319/00C07K 2319/50C12N 2770/36143A61K 39/12A61K 2039/55561A61K 2039/55555A61K 39/00
58
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Claims

Abstract

The present invention relates to immunogenic compositions comprising RSV F protein, methods for preparing compositions that contain RSV F protein ecto-domain polypeptides, and to certain engineered RSV F proteins and nucleic acids that encode the engineered RSV F proteins. Compositions prepared using the methods can contain RSV F protein ecto-domain polypeptides in a predominant or single desired form and conformation. The invention also relates to methods for inducing an immune response to RSV F.

Claims

exact text as granted — not AI-modified
1 . An immunogenic composition comprising one or more respiratory syncytial virus F (RSV F) polypeptides in which amino acids 100-150 are replaced with the amino acid sequence of SEQ ID NO:9, SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7; SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:91 or SEQ ID NO:92. 
     
     
         2 . The immunogenic composition of  claim 1 , wherein amino acids 100-150 of said RSV F are replaced with the amino acid sequence of SEQ ID NO:12. 
     
     
         3 . The immunogenic composition of  claim 1 , wherein amino acids 100-150 of said RSV F are replaced with the amino acid sequence of SEQ ID NO:9, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7; SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:13 or SEQ ID NO:92. 
     
     
         4 . The immunogenic composition of  claim 1 , wherein the RSV F is in the form of a monomer, trimer, or any combination thereof. 
     
     
         5 . The immunogenic composition of  claim 3 , wherein RSV F is a monomer, trimer, rosette, or any combination thereof. 
     
     
         6 . The immunogenic composition of any one of  claims 1 - 6 , wherein said RSV F comprises amino acids 23-99 and 151-524 of SEQ ID NO:1 or SEQ ID NO:2. 
     
     
         7 . An immunogenic composition comprising a polypeptide selected from the group consisting of SEQ ID NO:49, SEQ ID NO:68, SEQ ID NO:71, SEQ ID NO: 25, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:93 any of the foregoing sequences in which the signal peptide and/or HIS tag is omitted, and combinations thereof. 
     
     
         8 . The immunogenic composition of  claim 1 , further comprising an adjuvant. 
     
     
         9 . The immunogenic composition of  claim 8 , wherein the adjuvant is selected from the group consisting of an aluminum salt, a squalene-in-water emulsion, a benzonaphthyridine compound, a phospholipid compound, a small molecule immunepotentiator and a combination of any two or more of any of the foregoing. 
     
     
         10 . A recombinant respiratory syncytial virus F polypeptide (RSV F) in which amino acids 100-150 are replaced with the amino acid sequence of SEQ ID NO:9, SEQ ID NO:12, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:91 or SEQ ID NO:92. 
     
     
         11 . The recombinant RSV F of  claim 10 , wherein amino acids 100-150 of said RSV F are replaced with the amino acid sequence of SEQ ID NO:9, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7; SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:13 or SEQ ID NO:92. 
     
     
         12 . The recombinant RSV F of  claim 10 , wherein the RSV F is in the form of a monomer, trimer, or combination of monomers and trimers. 
     
     
         13 . The recombinant RSV F of  claim 11 , wherein the RSV F is in the form of a monomer, trimer, rosette of trimers or combinations thereof. 
     
     
         14 . A recombinant polypeptide selected from the group consisting of SEQ ID NO:49, SEQ ID NO:68, SEQ ID NO:71, SEQ ID NO: 25, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:93, any of the foregoing sequences in which the signal peptide and/or HIS tag is omitted, and combinations thereof. 
     
     
         15 . The recombinant polypeptide of  claim 10 , further comprising a heterologous oligomerization domain, an epitope, or a signal peptide. 
     
     
         16 . The recombinant polypeptide of  claim 15 , wherein said heterologous oligomerization domain is selected from the group comprising a trimerization domain from influenza hemagglutinin, from SARS spike, or from HIV gp41, NadA, modified GCN4, or ATCase. 
     
     
         17 . An isolated nucleic acid encoding the polypeptide of  claim 10 . 
     
     
         18 . A method of inducing an immune response in a subject to RSV F comprising administering an immunogenic composition of  claim 1  to the subject. 
     
     
         19 . A method for producing a composition comprising cleaved RSV F protein ecto-domain polypeptides, the method comprising:
 a) providing uncleaved RSV F protein ecto-domain polypeptides that contain a protease cleavage site that when cleaved produces F 1  and F 2  subunits, the amino acid sequence of said uncleaved soluble RSV F protein ecto-domain polypeptides comprising altered furin cleavage sites at positions 106-109 and 133-136, and said uncleaved soluble RSV F protein ecto-domain polypeptides are obtained from a cell that produces them uncleaved; and   b) cleaving the provided soluble RSV F protein ecto-domain polypeptides with a protease that cleaves said protease cleavage site, thereby producing a composition comprising cleaved soluble RSV F protein ecto-domain polypeptides.   
     
     
         20 . A composition comprising cleaved RSV F protein ecto-domain polypeptides produced using the method of  claim 19 . 
     
     
         21 . A method for producing a composition comprising uncleaved RSV F protein ecto-domain polypeptide monomers, trimers or a combination of monomers and trimers, the method comprising:
 a) providing a biological material that contains uncleaved RSV F protein ecto-domain polypeptides, the amino acid sequence of said uncleaved soluble RSV F protein ecto-domain polypeptides comprising altered furin cleavage sites at positions 106-109 and 133-136, and said uncleaved soluble RSV F protein ecto-domain polypeptides are secreted from a cell that produces them uncleaved; and   b) purifying uncleaved RSV F protein ecto-domain polypeptide monomers or trimers from the biological material, thereby producing the composition.   
     
     
         22 . A composition comprising soluble uncleaved RSV F protein ecto-domain polypeptide monomers or trimers produced using the method of  claim 21 . 
     
     
         23 . A method for producing a composition comprising uncleaved RSV F protein ecto-domain polypeptide monomers, trimers or a combination of monomers and trimers, the method comprising:
 a) providing a biological material that contains uncleaved RSV F protein ecto-domain polypeptides, wherein the amino acid sequence of the uncleaved RSV F protein ecto-domain polypeptide contains altered furin cleavage sites, lysine and arginine residues present between about position 101 and about position 161 are deleted or replaced with an amino acid that is not lysine or arginine, the RSV F protein ecto-domain polypeptides are obtained from a host cell that produces them uncleaved between about position 101 and about position 161, and the RSV F protein ecto-domain polypeptides are not cleaved between about position 101 and about position 161; and   b) purifying uncleaved RSV F protein ecto-domain polypeptide monomers, trimers or a combination of monomers and trimers from the biological material.   
     
     
         24 . A composition comprising soluble uncleaved RSV F protein ecto-domain polypeptides produced using the method of  claim 23 . 
     
     
         25 . A method for producing a composition comprising cleaved RSV F protein ecto-domain polypeptide monomers, trimers or a combination of monomers and trimers, the method comprising:
 a) providing biological material that contains cleaved RSV F protein ecto-domain polypeptides that contain an altered fusion peptide; and   b) purifying cleaved RSV F protein ecto-domain polypeptides from the biological material.   
     
     
         26 . A composition comprising soluble uncleaved RSV F protein ecto-domain polypeptides produced using the method of  claim 25 . 
     
     
         27 . A method for producing a composition comprising RSV F protein ecto-domain polypeptides, the method comprising:
 a) providing RSV F protein ecto-domain polypeptides that comprises an altered furin cleavage site at positions 133-136, and said soluble RSV F protein ecto-domain polypeptides are secreted from a cell that produces them in the form of an F 2  fragment that is associated with a subunit that comprises F 1  but is uncleaved at position 136/137; and   b) cleaving the provided RSV F protein ecto-domain polypeptides with a protease that cleaves RSV F protein ecto-domain at a site between positions 101 and 161, thereby producing said composition.   
     
     
         28 . A composition comprising cleaved RSV F protein ecto-domain polypeptides produced using the method of  claim 27 . 
     
     
         29 . A method for producing a composition comprising RSV F protein ecto-domain polypeptides, the method comprising:
 a) providing biological material that contains RSV F protein ecto-domain polypeptides that comprise an altered furin cleavage site at positions 133-136, and said soluble RSV F protein ecto-domain polypeptides are secreted from a cell that produces them in the form of an F 2  fragment that is associated with a subunit that comprises F 1  but is uncleaved at position 136/137, with the proviso that the altered furin cleavage site is not deletion of amino acids 131-134; and   b) purifying the RSV F protein ecto-domain polypeptides from the biological material, thereby producing the composition.   
     
     
         30 . A composition comprising RSV F protein ecto-domain polypeptide produced using the method of  claim 29 .

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