US4673574A
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Immunogenic conjugates
Assignee: University of Rochester
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Filing: 1983-07-05
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Granted: 1987-06-16
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Expires: 2003-07-05
Abstract
Abstract An immunogenic conjugate which is the reductive amination product of an immunogenic capsular polymer fragment having a reducing end and derived from a bacterial capsular polymer of a bacterial pathogen, and a bacterial toxin or toxoid. The invention also relates to methods for the preparation of the conjugates, a vaccine containing the conjugates which elicits effective levels of anti-capsular polymer antibodies in humans. Also disclosed are methods for inducing active immunization against systemic infection in young mammals caused by bacterial pathogens comprising the administration of an immunogenic amount of the above-described conjugate.
Inventors
- 👤 Porter W. Anderson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:10
CPC Classifications
A; A61; A61K; A61K39/00; A61K39/385; A61K39/02; A61K39/09; A61K39/092; A61K39/102; A61K2039/60; A61K2039/6031; A61K2039/6037; Y; Y10; Y10S; Y10S424/00; Y10S424/831; Y10S424/832
Claims Analysis
Total Claims: 53
Claim 1
Independent Claim
52 words
immunogenic conjugate comprising the reductve amination product of an immunogenic capsular polymer fragment having a chain length of from about 10 to about 30 monomeric units and a reducing end, which fragment is derived from the capsular polymer of a Streptococcus pneumoniae or Haemophilus influenzae bacterium, and a bacterial toxin or toxoid.
Claim 2
Dependent Claim
52 words
immunogenic conjugate comprising the reductve amination product of an immunogenic capsular polymer fragment having a chain length of from about 10 to about 30 monomeric units and a reducing end, which fragment is derived from the capsular polymer of a Streptococcus pneumoniae or Haemophilus influenzae bacterium, and a bacterial toxin or toxoid.
Claim 3
Dependent Claim
21 words
The immunogenic conjugate of claim 1, wherein the capsular polymer is immunogenic in mature humans and less immunogenic in infant humans.
Claim 4
Dependent Claim
18 words
The immunogenic conjugate of claim 1, wherein the reductive amination is performed in the persence of cyanoborohydride anions.
Claim 5
Dependent Claim
16 words
The immunogenic conjugate of claim 1, wherein the toxin or toxoid is diphtheria toxin or toxoid.
Claim 6
Dependent Claim
13 words
The immunogenic conjugate of claim 4, wherein the toxoid is CRM 197 .
Claim 7
Dependent Claim
16 words
The immunogenic conjugate of claim 1, wherein the toxin or toxoid is tetanus toxin or toxoid.
Claim 8
Dependent Claim
17 words
The immunogenic conjugate of claim 1, wherein the toxin or toxoid is a pseudomonas toxin or toxoid.
Claim 9
Dependent Claim
17 words
The immunogenic conjugate of claim 1, wherein the toxin or toxiod is a staphylococcus toxin or toxoid.
Claim 10
Dependent Claim
17 words
The immunogenic conjugate of claim 1, wherein the toxin or toxoid is a streptococcus toxin or toxoid.
Claim 11
Dependent Claim
16 words
The immunogenic conjugate of claim 1, wherein the toxin or toxoid is pertussis toxin or toxoid.
Claim 12
Dependent Claim
17 words
The immunogenic conjugate of claim 1, wherein the toxin or toxoid is Escherichia coli toxin or toxoid.
Claim 13
Dependent Claim
15 words
The immunogenic conjugate of claim 1, wherein the bacterial pathogen is Haemophilus influenzae type b.
Claim 14
Dependent Claim
15 words
The immunogenic conjugate of claim 1, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 3.
Claim 15
Dependent Claim
15 words
The immunogenic conjugate of claim 1, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 6.
Claim 16
Dependent Claim
15 words
The immunogenic conjugate of claim 1, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 12.
Claim 17
Dependent Claim
15 words
The immunogenic conjugate of claim 1, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 14.
Claim 18
Dependent Claim
15 words
The immunogenic conjugate of claim 1, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 19.
Claim 19
Dependent Claim
15 words
The immunogenic conjugate of claim 1, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 23.
Claim 20
Dependent Claim
15 words
The immunogenic conjugate of claim 1, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 51.
Claim 21
Dependent Claim
15 words
The immunogenic conjugate of claim 5, wherein the bacterial pathogen is Haemophilis influenzae type b.
Claim 22
Dependent Claim
15 words
The immunogenic conjugate of claim 5, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 6.
Claim 23
Dependent Claim
15 words
The immunogenic conjugate of claim 5, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 14.
Claim 24
Dependent Claim
15 words
The immunogenic conjugate of claim 5, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 19.
Claim 25
Dependent Claim
15 words
The immunogenic conjugate of claim 5, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 23.
Claim 26
Dependent Claim
18 words
The immunogenic conjugate of claim 1, wherein the fragment is derived from the capsular polymer by oxidative cleavage.
Claim 27
Dependent Claim
17 words
The immunogenic conjugate of claim 1, wherein the fragment is derived from the capsular polymer by periodate.
Claim 28
Dependent Claim
21 words
The immunogenic conjugate of claim 1, wherein the fragment is derived from the capsular polymer by hydrolysis of a glycosidic linkage.
Claim 29
Dependent Claim
12 words
The immunogenic conjugate of claim 27, wherein the hydrolysis is accomplished enzymatically.
Claim 30
Dependent Claim
12 words
The immunogenic conjugate of claim 27, wherein the hydrolysis is accomplished chemically.
Claim 31
Dependent Claim
13 words
The immunogenic conjugate of claim 27, wherein the hydrolysis is accomplished by acid.
Claim 32
Dependent Claim
22 words
The immunogenic conjugate of claim 12, wherein the fragment elutes on a column of Bio-Gel P-10 at a Ve/Vo ratio of ≦1.08.
Claim 33
Dependent Claim
22 words
The immunogenic conjugate of claim 12, wherein the fragment elutes on a column of Bio-Gel P-10 at a Ve/Vo ratio of 1.09-1.38.
Claim 34
Dependent Claim
22 words
The immunogenic conjugate of claim 12, wherein the fragment elutes on a column of Bio-Gel P-10 at a Ve/Vo ratio of 1.39-1.99.
Claim 35
Dependent Claim
55 words
An immunogenic conjugate comprising a formalin treated reductive amination product of an immunogenic capsular polymer fragment having a chain length of from about 10 to about 30 monomeric units and a reducing end, which fragment is derived from the capsular polymer of a Streptococcus pneumoniae or Haemophilus influenzae bacterium, and a bacterial toxin or toxoid.
Claim 36
Dependent Claim
55 words
An immunogenic conjugate comprising a formalin treated reductive amination product of an immunogenic capsular polymer fragment having a chain length of from about 10 to about 30 monomeric units and a reducing end, which fragment is derived from the capsular polymer of a Streptococcus pneumoniae or Haemophilus influenzae bacterium, and a bacterial toxin or toxoid.
Claim 37
Dependent Claim
13 words
The immunogenic conjugate of claim 34, wherein the bacterial toxoid is diptheria toxoid.
Claim 38
Dependent Claim
13 words
The immunogenic conjugate of claim 35, wherein the Toxoid is CRM 197 .
Claim 39
Dependent Claim
17 words
The immunogenic conjugate of claim 34, wherein the bacterial toxin or toxoid is tetanus toxin or toxoid.
Claim 40
Dependent Claim
45 words
An immunogenic conjugate of (1) a PRP polysaccharide fragment having reducing terminal groups derived from the capsular polysaccharide of Haemophilus influenzae type b by selective acidic hydrolysis of a portion of the ribosyl ribitol linkages therein and (2) the diphtheria toxin protein CRM 197 .
Claim 41
Dependent Claim
45 words
An immunogenic conjugate of (1) a PRP polysaccharide fragment having reducing terminal groups derived from the capsular polysaccharide of Haemophilus influenzae type b by selective acidic hydrolysis of a portion of the ribosyl ribitol linkages therein and (2) the diphtheria toxin protein CRM 197 .
Claim 42
Dependent Claim
16 words
The conjugate of claim 38 prepared by the reductive amination of the PRP fragment and protein.
Claim 43
Dependent Claim
15 words
The conjugate of claim 38 prepared by reductive amination in the presence of cyanoborohydride anions.
Claim 44
Dependent Claim
22 words
The conjugate of claim 38 wherein said PRP fragment elutes from a column of Bio-Gel P-10 at a Ve/Vo ratio of ≦1.08.
Claim 45
Dependent Claim
22 words
The conjugate of claim 38 wherein said PRP fragment elutes from a column of Bio-Gel P-10 at a Ve/Vo ratio of 1.09-1.38.
Claim 46
Dependent Claim
22 words
The conjugate of claim 38 wherein said PRP fragment elutes from a column of Bio-Gel P-10 at a Ve/Vo ratio of 1.39-1.99.
Claim 47
Dependent Claim
22 words
The conjugate of claim 38 wherein said PRP fragment elutes from a column of Bio-Gel P-10 at a Ve/Vo ratio of 2.0-2.4.
Claim 48
Dependent Claim
19 words
A vaccine that elicits effective levels of anti-capsular polymer antibodies in humans, comprising: the immunogenic conjugate of claim 1.
Claim 49
Dependent Claim
25 words
A method for actively immunizing humans against a bacterial pathogen having a capsular polymer, comprising: administering an effective amount of the vaccine of claim 45.
Claim 50
Dependent Claim
29 words
A vaccine that elicits effective levels of anti-PRP antibody formations in young warm-blooded mammals comprising an immunogenic amount of the conjugate of claim 41 and a pharmaceutically acceptable carrier.
Claim 51
Dependent Claim
28 words
A vaccine that elicits effective levels anti-PRP antibody formations in young warm-blooded mammals comprising an immunogenic amount of the conjugate of claim 42 and a pharmaceutically acceptable carrier.
Claim 52
Dependent Claim
15 words
The immunogenic conjugate of claim 5, wherein the bacterial pathogen is Streptoccoccus pneumoniae serotype 3.
Claim 53
Dependent Claim
15 words
The immunogenic conjugate of claim 5, wherein the bacterial pathogen is Streptococcus pneumoniae serotype 51.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1990-06-15 | 1990-12-15 | 1991-06-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-06-15 | 1994-12-15 | 1995-06-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-06-15 | 1998-12-15 | 1999-06-16 | $7700.00 | Window Closed / Lapsed |