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CN-121971595-A - Improvements in immunogenic conjugates

CN121971595ACN 121971595 ACN121971595 ACN 121971595ACN-121971595-A

Abstract

Various improvements are disclosed relating to immunogenic conjugates comprising a carrier polypeptide and a saccharide antigen covalently bound to the carrier polypeptide through an unnatural amino acid residue in the carrier polypeptide.

Inventors

  • FELLMAN JACOB
  • J. HEIINRISHIS
  • W.CHEN

Assignees

  • VAXCYTE公司

Dates

Publication Date
20260505
Application Date
20190701
Priority Date
20180704

Claims (8)

  1. 1. A method of preparing a pharmaceutical composition, wherein the pharmaceutical composition comprises two or more different immunogenic conjugates and an aluminum salt adjuvant, wherein (I) Each of the immunogenic conjugates comprises a carrier polypeptide and a saccharide antigen, and (Ii) The saccharide antigen is covalently bound to the carrier polypeptide through an unnatural amino acid residue in the carrier polypeptide, and The method comprises any one of the following steps: (a) Adsorbing each of said immunogenic conjugates separately to an aluminum salt adjuvant, and mixing the individual adsorbed conjugates together; (b) Each of the immunogenic conjugates is sequentially adsorbed to the aluminum salt adjuvant.
  2. 2. The method of claim 1, wherein the carrier polypeptide: (i) Has at least 90% sequence identity to SEQ ID NO. 1; (ii) Does not contain Arg-Arg dipeptide sequence, or (Iii) Has sequence identity to SEQ ID NO. 1 and comprises unnatural amino acid (nnAA) residues that replace K33, K212, K244, K264, K385 and K526 in SEQ ID NO. 1.
  3. 3. The method of claim 1, wherein the carrier polypeptide comprises the amino acid sequence of SEQ ID No. 4.
  4. 4. The method of claim 2, wherein the nnAA residue comprises a functional group adapted to "click" a chemical reaction with a functional group on the saccharide antigen.
  5. 5. The method of claim 2, wherein each of the nnAA residues is 2-amino-3- (4- (azidomethyl) phenyl) propionic acid (pAMF).
  6. 6. The method of claim 1, wherein the saccharide antigen is a bacterial capsular saccharide selected from the group consisting of streptococcus pneumoniae, neisseria meningitidis, haemophilus influenzae, streptococcus pyogenes, streptococcus agalactiae, and porphyromonas gingivalis.
  7. 7. The method of claim 1, wherein the saccharide antigen is a capsular saccharide from a streptococcus pneumoniae serotype selected from the group consisting of 1, 2,3, 4, 5, 6A, 6B, 7C, 7F, 8, 9V, 9N, 10A, 11A, 12F, 13, 14, 15A, 15B, 16, 17F, 18C, 19A, 19F, 20, 22F, 23A, 23B, 31, 33F, and 35B.
  8. 8. The method of claim 1, wherein the aluminum salt adjuvant is an aluminum phosphate adjuvant.

Description

Improvements in immunogenic conjugates The present application is a divisional application of patent application No. 2019800441698, entitled "improvement of immunogenic conjugates" in china and application date 2019, 7-1 (PCT application No. PCT/US 2019/040131). Cross Reference to Related Applications The present application claims the benefit of priority from U.S. patent application Ser. No. 62/693,981 filed on 7/4 at 2018, the contents of which are incorporated herein by reference in their entirety. Merging of electronic text files submitted with text The content of the text file submitted electronically herewith is incorporated herein by reference in its entirety, a computer-readable format copy of the sequence listing (filename: STRO 005_01wo _ seqlist _ st25.Txt, recording date: 7 months 1 in 2019, file size: about 23 kilobytes). Background The immune response to a "weak" carbohydrate antigen may be enhanced by conjugation with a known "strong" carrier polypeptide antigen such as diphtheria toxoid, tetanus toxoid, haemophilus influenzae (h.influenzae) protein D or CRM 197. WO 2018/126229 (SutroVax, inc. Of Foster City, california (SutroVax, inc., foster City, california)) discloses methods, compositions and techniques for producing conjugated vaccine antigens using carrier polypeptides comprising unnatural amino acids (nnAA). The orthogonal ligation chemistry by nnAA allows conjugation of antigens to carrier polypeptides to produce immunogenic conjugates that can be used for immunization. It is an object of the present invention to provide variations and improvements in such methods, compositions and techniques. The variants and modifications described below may be applied to or combined with any of the methods, compositions or techniques disclosed in WO 2018/126229 or U.S. provisional patent application serial nos. 62/693,978 and 62/693,981 (all filed on 7.4 of 2018). The aforementioned patent application is incorporated herein by reference in its entirety. Disclosure of Invention In one embodiment, a sterile container (e.g., vial) is provided that contains a pharmaceutical composition comprising an immunogenic conjugate comprising a carrier polypeptide and a saccharide antigen, wherein the saccharide antigen is covalently bound to the carrier polypeptide through an unnatural amino acid residue in the carrier polypeptide. The container may contain a unit dose of the pharmaceutical composition. Sterile glass containers are preferred. In another embodiment, a delivery device (e.g., syringe, nebulizer, inhaler, skin patch, etc.) is provided that contains a pharmaceutical composition comprising an immunogenic conjugate comprising a carrier polypeptide and a saccharide antigen, wherein the saccharide antigen is covalently bound to the carrier polypeptide through an unnatural amino acid residue in the carrier polypeptide. The delivery device may contain a unit dose of the pharmaceutical composition. The delivery device may be used to administer the pharmaceutical composition to a mammalian subject. In another embodiment, a hermetically sealed container is provided that contains a pharmaceutical composition comprising an immunogenic conjugate comprising a carrier polypeptide and a saccharide antigen, wherein the saccharide antigen is covalently bound to the carrier polypeptide through an unnatural amino acid residue in the carrier polypeptide. Suitable containers for sealing include, for example, vials. The contents are preferably sterile when hermetically sealed. In another embodiment, a syringe is provided that contains 0.25-0.75 mL (e.g., 0.3-0.75 mL, preferably 0.5 mL) of a pharmaceutical composition comprising two or more different immunogenic conjugates, each immunogenic conjugate comprising a carrier polypeptide and a saccharide antigen, wherein the saccharide antigen is covalently bound to the carrier polypeptide through an unnatural amino acid residue in the carrier polypeptide. In another embodiment, a pharmaceutical composition is provided comprising two or more different immunogenic conjugates, wherein (i) each immunogenic conjugate comprises a carrier polypeptide and a saccharide antigen, wherein the saccharide antigen is covalently bound to the carrier polypeptide via an unnatural amino acid residue in the carrier polypeptide, (ii) the aluminum salt adjuvant is an aluminum hydroxide or aluminum phosphate adjuvant, and (iii) the pharmaceutical composition has a volume of 0.25-0.75 mL (e.g., 0.3-0.75 mL, preferably 0.5 mL). In another embodiment, a pharmaceutical composition is provided comprising two or more different immunogenic conjugates and an aluminum phosphate adjuvant, wherein (i) each immunogenic conjugate comprises a carrier polypeptide and a saccharide antigen, wherein the saccharide antigen is covalently bound to the carrier polypeptide through an unnatural amino acid residue in the carrier polypeptide, and (ii) the concentration of aluminum ions in the composition is <300 μg/mL (e.g.