# US 9,040,055 B2 · Conjugation of streptococcal capsular saccharides

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- Number: US 9,040,055 B2
- Document ID: US9040055B2
- Status: Granted
- Kind: B2
- Application number: 13/912,919
- Filed: 2013-06-07
- Published: 2013-11-07
- Granted: 2015-05-26
- Earliest claimed: 2005-02-01
- Assignees: Novartis Vaccines and Diagnostics, Inc.
- Applicants: Novartis Vaccines and Diagnostics SRL
- Inventors: Francesco Berti
- Web page: https://patentgrep.com/patent/US9040055B2

## CPC

- A61K 39/092: {Streptococcus}
- A61K 39/09: {Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus}, streptococcus
- A61K 39/385: Haptens or antigens, bound to carriers
- A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof
- A61K 47/6415: {Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins}
- A61K 47/643: {Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]}
- A61K 47/646: {the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines}
- A61P 31/04: Antibacterial agents
- A61P 37/04: Immunostimulants
- A61P 39/04: Chelating agents
- C07K 14/315: from Streptococcus (G), e.g. Enterococci
- A61K 2039/575: {humoral response}
- A61K 2039/6031: {Proteins}
- A61K 2039/6037: {Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]}
- A61K 2039/6068: {Other bacterial proteins, e.g. OMP}
- A61K 2039/6081: {Albumin; Keyhole limpet haemocyanin [KLH]}
- A61K 2039/627: {characterised by the linker}
- A61K 2039/64: {characterised by the architecture of the carrier-antigen complex, e.g. repetition of carrier-antigen units}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Three conjugation methods for use with the capsular saccharide of Streptococcus agalactiae. In the first method, reductive animation of oxidized sialic acid residue side chains is used, but the aldehyde groups are first aminated, and then the amine is coupled to a carrier via a linker. In the second method, sialic acid residues and/or N-acetyl-glucosamine residues are de-N-acetylated to give amine groups, and the amine groups are coupled to a carrier protein via a linker. In the third method, linkage is via galactose residues in the capsular saccharide rather than sialic acid residues, which can conveniently be achieved using galactose oxidase.

## Claims

### Claim 1

A conjugated saccharide comprising a Streptococcus agalactiae capsular saccharide moiety joined to a carrier via a linker moiety, wherein:
the linker moiety is attached to a sialic acid residue in the capsular saccharide moiety,
the capsular saccharide is from a group B streptococcus (GBS) bacterium having a serotype selected from the group consisting of Ia, Ib, II, III, V, and combinations thereof,
the capsular saccharide is partially or fully deacetylated,
the carrier is the GBS protein antigen GBS80, and
a weight ratio of capsular saccharide to GBS protein antigen is from 1:5 to 5:1.

### Claim 2

A conjugated saccharide comprising a Streptococcus agalactiae capsular saccharide moiety joined to a carrier via a linker moiety, wherein:
the linker moiety is attached to a sialic acid residue in the capsular saccharide moiety,
the capsular saccharide is from a group B streptococcus (GBS) bacterium having a serotype selected from the group consisting of Ia, Ib, II, III, V, and combinations thereof,
the capsular saccharide is partially or fully deacetylated,
the carrier is the GBS protein antigen GBS80, and
aldehyde groups are introduced into between 5% and 50% of the sialic acid monosaccharide units of the capsular saccharide.

### Claim 3

A conjugated saccharide of comprising a Streptococcus agalactiae capsular saccharide moiety joined to a carrier via a linker moiety, wherein:
the linker moiety is attached to a sialic acid residue in the capsular saccharide moiety,
the capsular saccharide is from a group B streptococcus (GBS) bacterium having a serotype selected from the group consisting of Ia, Ib, II, III, V, and combinations thereof,
the capsular saccharide is partially or fully deacetylated,
the carrier is the GBS protein antigen GBS80,
the linker moiety is bonded to the sialic acid residue in the capsular saccharide moiety and bonded to the carrier via a terminal —NH— or a terminal —C(O)— of the linker moiety, and
the linker moiety has the formula —NH—C(O)—(CH2)n—C(O)—,
wherein n is an integer from 1-9.

### Claim 4

A conjugated saccharide comprising a Streptococcus agalactiae capsular saccharide moiety joined to a carrier via a linker moiety, wherein:
the linker moiety is attached to a sialic acid residue in the capsular saccharide moiety,
the capsular saccharide is from a group B streptococcus (GBS) bacterium having a serotype selected from the group consisting of Ia, Ib, II, III, V, and combinations thereof,
the capsular saccharide is partially or fully deacetylated,
the carrier is the GBS protein antigen GBS80,
the linker moiety is bonded to the sialic acid residue in the capsular saccharide moiety and bonded to the carrier via a terminal —NH— or a terminal —C(O)— of the linker moiety, and
the linker moiety has the formula —C(O)—(CH2)nαC(O)—, wherein n is an integer from 1-10.

### Claim 5 (depends on 1)

A composition comprising the conjugated saccharide of claim 1 and one or more further antigens.

### Claim 6 (depends on 5)

The composition of claim 5, wherein the one or more further antigens include an antigen from a non-GBS pathogen.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the antigen from the non-GBS pathogen is a diphtheria antigen.

### Claim 8 (depends on 5)

The composition of claim 5, further comprising an adjuvant.

### Claim 9 (depends on 5)

A method for eliciting an immune response in a subject, the method comprising administering to the subject the composition of claim 5 in an amount sufficient to elicit the immune response.

### Claim 10 (depends on 9)

The method of claim 9, wherein the immune response comprises the generation of antibodies in the subject.