Patent FR2510394A1 successfully refreshed from Google Patents.
US4695624A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Covalently-modified polyanionic bacterial polysaccharides, stable covalent conjugates of such polysaccharides and immunogenic proteins with bigeneric spacers, and methods of preparing such polysaccharides and conjugates and of confirming covalency
Assignee: Merck and Co Inc
•
Filing: 1985-04-04
•
Granted: 1987-09-22
•
Expires: 2005-04-04
Abstract
Abstract Covalently modified bacterial polysaccharides and proteins; covalent conjugates of such polysaccharides linked by a bigeneric spacer, which permits proof of covalency and facilitates purification of conjugated materials, with immunogenic bacterial membrane or other proteins, which conjugates are useful components of bacterial vaccines; and methods of preparing such polysaccharides, proteins and conjugates and of confirming the covalency of the linkage between polysaccharides and proteins.
Inventors
- 👤 Stephen Marburg
- 👤 Richard L. Tolman
- 👤 Peter J. Kniskern
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 04:05
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/569; A; A61; A61K; A61K39/00; A61K39/385; A61K39/39; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/61; A61K47/62; A61K47/65; C; C07; C07K; C07K17/00; C07K17/02; C07K17/06; C07K17/10; G01N33/531; A61K2039/555; A61K2039/55511; A61K2039/55516; A61K2039/55583; A61K2039/60; A61K2039/6031; A61K2039/62; A61K2039/627; Y; Y10; Y10S; Y10S424/00; Y10S424/831
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
159 words
Stable, covalently-coupled polysaccharide-protein conjugates comprising polyanionic bacterial polysaccharides having acid groups and immunogenic proteins coupled through bigeneric spacers, containing thioether bonds, which may be represented by the formula A-E-S-B, wherein E is ##STR35## where R is H or CH 3 ; A is ##STR36## where m is 0 to 4, n is 0 to 3, W is O or NH, and Y is CH 2 , O, S, NR', or CHCO 2 H, where R' is H or C 1 - or C 2 -alkyl, such that when Y is CH 2 , then both m and n are not equal to zero, and when Y is O or S, then m is 2, 3 or 4 and n is 2 or 3 and B is ##STR37## where p is 1 to 3, q is 0 to 2, Z is NH 2 , ##STR38## CO 2 H or H, and D is ##STR39## where R' is as defined above.
Claim 2
Dependent Claim
159 words
Stable, covalently-coupled polysaccharide-protein conjugates comprising polyanionic bacterial polysaccharides having acid groups and immunogenic proteins coupled through bigeneric spacers, containing thioether bonds, which may be represented by the formula A-E-S-B, wherein E is ##STR35## where R is H or CH 3 ; A is ##STR36## where m is 0 to 4, n is 0 to 3, W is O or NH, and Y is CH 2 , O, S, NR', or CHCO 2 H, where R' is H or C 1 - or C 2 -alkyl, such that when Y is CH 2 , then both m and n are not equal to zero, and when Y is O or S, then m is 2, 3 or 4 and n is 2 or 3 and B is ##STR37## where p is 1 to 3, q is 0 to 2, Z is NH 2 , ##STR38## CO 2 H or H, and D is ##STR39## where R' is as defined above.
Claim 3
Dependent Claim
19 words
Stable, covalently-coupled polysaccharide-protein conjugates according to claim 1, wherein the bigeneric spacers may be represented by the formula, ##STR40##
Claim 4
Dependent Claim
35 words
Polysaccharide-protein conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is selected from the group consisting of Haemophilus influenzae type b polysaccharide, and Streptococcus pneumoniae types 6B, 19F and 23F polysaccharides.
Claim 5
Dependent Claim
21 words
Polysaccharide-protein conjugates according to claim 1, wherein the immunogenic protein is a meningococcal B serotype outer membrane protein or edestin protein.
Claim 6
Dependent Claim
29 words
A stable, covalently-coupled polysaccharide-protein conjugate consisting of an Haemophilus influenzae type b polysaccharide coupled through a spacer of the formula: ##STR41## to a meningococcal B serotype outer membrane protein.
Claim 7
Dependent Claim
29 words
A stable, covalently-coupled polysaccharide-protein conjugate consisting of an Haemophilus influenzae type b polysaccharide coupled through a spacer of the formula: ##STR41## to a meningococcal B serotype outer membrane protein.
Claim 8
Dependent Claim
41 words
Polysaccharide-protein conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is pneumococcal type 6B polysaccharide, the immunogenic protein is a meningococcal B serotype outer membrane protein and the bigeneric spacer may be represented by the formula, ##STR42##
Claim 9
Dependent Claim
41 words
Polysaccharide-protein conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is pneumococcal type 19F polysaccharide, the immunogenic protein is a meningococcal B serotype outer membrane protein and the bigeneric spacer may be represented by the formula, ##STR43##
Claim 10
Dependent Claim
41 words
Polysaccharide-protein conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is pneumococcal type 23F polysaccharide, the immunogenic protein is a meningococcal B serotype outer membrane protein and the bigeneric spacer may be represented by the formula, ##STR44##
Claim 11
Dependent Claim
50 words
A composition comprising an immunologically-effective amount for either active or passive protection of mammalion species from the bacteremia caused by the cognate organism, of stable, covalently-coupled polysaccharide-protein conjugates according to claim 1, antisera derived from said conjugates, or gamma-globulin or other antibody-containing fractions of said antisera, and a pharmaceutically-acceptable carrier.
Claim 12
Dependent Claim
10 words
A composition according to claim 9, further comprising an adjuvant.
Claim 13
Dependent Claim
113 words
A composition according to claim 9 or claim 10, wherein the polysaccharide-protein conjugates comprise one or more members of the group consisting of an Haemophilus influenzae type b polysaccharide coupled through a bigeneric spacer of the formula, ##STR45## to a meningococcal B serotype outer membrane protein; a pneumococcal type 6B polysaccharide coupled through a bigeneric spacer, of the formula, ##STR46## to a meningococcal B serotype outer membrane protein; a pneumococcal type 19F polysaccharide coupled through a bigeneric spacer of the formula, ##STR47## to a meningococcal B serotype outer membrane protein; and a pneumococcal type 23F polysaccharide coupled through a bigeneric spacer of the formula, ##STR48## to a meningococcal B serotype outer membrane protein.
Claim 14
Dependent Claim
36 words
A composition according to claim 11, wherein an immunologically-effective amount is an amount of each of the conjugates in the composition such that each conjugate contains from 2-50 μg of the polysaccharide in the conjugate form.
Claim 15
Dependent Claim
12 words
A composition according to claim 11, wherein the mammalian species is humans.
Claim 16
Dependent Claim
58 words
A composition according to claim 12, wherein an immunologically-effective amount is an amount of each of the conjugates in the composition such that each conjugate contains 25 μg of the polysaccharide in the conjugate form for conjugates of pneumococcal polysaccharides and 10 μg of the polysaccharide in the conjugate form for conjugates of Haemophilus influenzae type b polysaccharide.
Claim 17
Independent Claim
69 words
A method of treating mammalian species against the bacteremia of the cognate organisms, which comprises administering to said species an immunologically-effective amount of a composition comprising one or more types of polysaccharide-protein conjugates comprising bacterial capsular polysaccharides having acid groups coupled through bigeneric spacers, containing thioether bonds, to immunogenic proteins, and a member of the group consisting of a pharmaceutically-acceptable carrier, an adjuvant, and a pharmaceutically-acceptable carrier and adjuvant.
Claim 18
Independent Claim
69 words
A method of treating mammalian species against the bacteremia of the cognate organisms, which comprises administering to said species an immunologically-effective amount of a composition comprising one or more types of polysaccharide-protein conjugates comprising bacterial capsular polysaccharides having acid groups coupled through bigeneric spacers, containing thioether bonds, to immunogenic proteins, and a member of the group consisting of a pharmaceutically-acceptable carrier, an adjuvant, and a pharmaceutically-acceptable carrier and adjuvant.
Claim 19
Dependent Claim
114 words
A method of treating mammalian species according to claim 15, wherein said polysaccharide-protein conjugates comprise one or more members of the group consisting of an Haemophilus influenzae type b polysaccharide coupled through a bigeneric spacer of the formula, ##STR49## to a meningococcal B serotype outer membrane protein; a pneumococcal type 6B polysaccharide coupled through a bigeneric spacer of the formula, ##STR50## to a meningococcal B serotype outer membrane protein, a pneumococcal type 19F polysaccharide coupled through a bigeneric spacer of the formula, ##STR51## to a meningococcal B serotype outer membrane protein; and a pneumococcal type 23F polysaccharide coupled through a bigeneric spacer of the formula, ##STR52## to a meningococcal B serotype outer membrane protein.
Claim 20
Dependent Claim
73 words
A method of treating mammalian species according to claim 15, wherein the species to be treated is human infants and children, and the effective amount of the composition in a single dose is an amount corresponding to 25 μg of the polysaccharide in the conjugate form for conjugates of pneumococcal polysaccharides and 10 μg of the polysaccharide in the conjugate form for conjugates of the Haemophilus influenzae type b polysaccharide-protein conjugates being administered.
Claim 21
Dependent Claim
66 words
A method of treating mammalian species according to claim 17, wherein one or two additional booster compositions of an amount of a polysaccharide-protein conjugate comprising an Haemophilus influenzae type b polysaccharide coupled through a bigeneric spacer of the formula, ##STR53## to a meningococcal B serotype outer membrane protein corresponding to 10 μg of polysaccharide in the conjugate form may be administered to human infants and children.
Claim 22
Dependent Claim
48 words
Polysaccharide-protein conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is a Group B Streptococcus type Ia, Ib, II or III polysaccharide, the immunogenic protein is a meningococcal B serotype outer membrane protein and the bigeneric spacer may be represented by the formula, ##STR54##
Claim 23
Dependent Claim
41 words
Polysaccharide-prote:n conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is an Escherichia coli Kl polysaccharide, the immunogenic protein is a meningococcal B serotype outer membrane protein and the bigeneric spacer may be represented by the ##STR55##
References Cited (Backward Citations)
US3759890A
Cited
US4185090A
Cited
US3969287A
Cited
US4175073A
Cited
US4275000A
Cited
US4356170A
Cited
US4451446A
Cited
US4459286A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1990-09-21 | 1991-03-23 | 1991-09-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-09-21 | 1995-03-23 | 1995-09-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-09-21 | 1999-03-23 | 1999-09-22 | $7700.00 | Window Closed / Lapsed |