US5208008A
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Regioselective chemical modification of monoclonal antibodies
Assignee: University of Pittsburgh
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Filing: 1990-11-14
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Granted: 1993-05-04
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Expires: 2010-11-14
Abstract
Abstract A method of selectively modifying an immunoglobulin having at least one Fab region and at least one Fc region, each region having an isoelectric point wherein said isoelectric point of the Fab fragment of said immunoglobulin is different than the isoelectric point of the Fc fragment of the immunoglobulin, said method comprising modification of the immunoglobulin at a pH between the respective isoelectric points of the Fab and Fc fragments of the immunoglobulin.
Inventors
- 👤 Girish Ranadive
- 👤 Howard S. Rosenzweig
- 👤 Michael Epperly
- 👤 William Bloomer
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 19:28
CPC Classifications
C; C07; C07K; C07K1/00; C07K1/107; C07K1/1072; C07K1/1077; C07K1/003; C07K16/00
Claims Analysis
Total Claims: 43
Claim 1
Independent Claim
78 words
A method of selectively modifying an immunoglobulin having at least one Fab region and at least one Fc region, each region having an isoelectric point wherein said isoelectric point of the Fab fragment of said immunoglobulin is different than the isoelectric point of the Fc fragment of immunoglobulin, said method comprising modification of the Fc region amino groups of the immunoglobulin at a pH between the respective isoelectric point of the Fab and Fc fragments of the immunoglobulin.
Claim 2
Independent Claim
78 words
A method of selectively modifying an immunoglobulin having at least one Fab region and at least one Fc region, each region having an isoelectric point wherein said isoelectric point of the Fab fragment of said immunoglobulin is different than the isoelectric point of the Fc fragment of immunoglobulin, said method comprising modification of the Fc region amino groups of the immunoglobulin at a pH between the respective isoelectric point of the Fab and Fc fragments of the immunoglobulin.
Claim 3
Dependent Claim
11 words
The method of claim 1, wherein said immunoglobulin is an antibody.
Claim 4
Dependent Claim
12 words
The method of claim 2, wherein said immunoglobulin is a monoclonal antibody.
Claim 5
Dependent Claim
11 words
The method of claim 3, wherein said monoclonal antibody is B72.3.
Claim 6
Dependent Claim
14 words
The method of claim 3, wherein said monoclonal antibody is human antiglioblastoma monoclonal antibody.
Claim 7
Dependent Claim
33 words
The method of claim 1, wherein the difference of values of said isoelectric points of the Fab and Fc fragments of said immunoglobulin is in the range of about 1.0 to about 2.0.
Claim 8
Dependent Claim
32 words
The method of claim 1, wherein the difference of the values of said isoelectric points of the Fab and Fc fragments of said immunoglobulin is greater than or equal to about 1.0.
Claim 9
Dependent Claim
23 words
The method of claim 1, wherein said modification comprises attachment of a compound containing a radionuclide suitable for gamma imaging to said immunoglobulin.
Claim 10
Dependent Claim
17 words
The method of claim 8, wherein said radionuclide comprises the group consisting of the halogens and astatine.
Claim 11
Dependent Claim
10 words
The method of claim 9, wherein said radionuclide is iodine-125.
Claim 12
Dependent Claim
16 words
The method of claim 1, wherein said modification comprises attachment of a toxin to said immunoglobulin.
Claim 13
Dependent Claim
13 words
The method of claim 11, wherein said toxin is diphtheria toxin or ricin.
Claim 14
Dependent Claim
16 words
The method of claim 1, wherein said modification comprises attachment of a drug to said immunoglobulin.
Claim 15
Dependent Claim
21 words
The method of claim 13, wherein said drug is a chemotherapeutic agent selected from the group consisting of methoxrexate and vinblastine.
Claim 16
Dependent Claim
17 words
The method of claim 1, wherein said modification comprises attachment of a fluorescent agent to said immunoglobulin.
Claim 17
Dependent Claim
11 words
The method of claim 15, wherein said fluorescent agent is SITS.
Claim 18
Dependent Claim
11 words
The method of claim 15, wherein said fluorescent agent is FITC.
Claim 19
Dependent Claim
34 words
The method of claim 1 wherein said method comprises modification of basic amino groups of the immunogloublin at a pH between the respective isoelectric points of the Fab and Fc fragments of the immunoglobulin.
Claim 20
Dependent Claim
33 words
The method of claim 10 wherein said method comprises modification of lysine groups of the immunoglobulin at a pH between the respective isoelectric points of the Fab and Fc fragments of the immunoglobulin.
Claim 21
Independent Claim
59 words
The method of enhancing the biodistribution of immunoglobulin having a Fab region and an Fc region for localization in a target, comprising exposing a mammalian subject to immunoglobulin that has been chemically modified at only the Fc region amino groups of the immunoglobulin at a pH between the isoelectric points of the Fab and Fc fragments of the immunoglobulin.
Claim 22
Independent Claim
59 words
The method of enhancing the biodistribution of immunoglobulin having a Fab region and an Fc region for localization in a target, comprising exposing a mammalian subject to immunoglobulin that has been chemically modified at only the Fc region amino groups of the immunoglobulin at a pH between the isoelectric points of the Fab and Fc fragments of the immunoglobulin.
Claim 23
Dependent Claim
34 words
The method of claim 20, wherein the difference of the values of said isoelectric points of the Fab and Fc fragments of said immunoglobulin is in the range of about 1.0 to about 2.0.
Claim 24
Dependent Claim
32 words
The method of claim 20, wherein the difference of the values of said isoelectric points of the Fab and Fc fragments of said immunoglobulin is greater than or equal to about 1.0.
Claim 25
Dependent Claim
11 words
The method of claim 20, wherein said immunoglobulin is an antibody.
Claim 26
Dependent Claim
12 words
The method of claim 23, wherein said antibody is a monoclonal antibody.
Claim 27
Dependent Claim
20 words
The method of claim 20, wherein said chemical modification comprises attachment of a compound containing a radionuclide to said immunoglobulin.
Claim 28
Dependent Claim
10 words
The method of claim 25, wherein said compound contains iodine-125.
Claim 29
Dependent Claim
17 words
The method of claim 20, wherein said chemical modification comprises attachment of a toxin to said immunoglobulin.
Claim 30
Dependent Claim
17 words
The method of claim 20, wherein said chemical modification comprises attachment of a drug to said immunoglobulin.
Claim 31
Dependent Claim
27 words
The method of claim 28, wherein said modification is performed at a pH at about the midpoint of the pI values of the Fc and Fab fragments.
Claim 32
Dependent Claim
12 words
The method of claim 28, wherein said immunoglobulin is a monoclonal antibody.
Claim 33
Dependent Claim
18 words
The method of claim 20, wherein said chemical modification comprises attachment of a fluroescent agent to said immunoglobulin.
Claim 34
Dependent Claim
29 words
The method of claim 20 wherein said method comprises exposing a mammalian subject to immunoglobulin that has been chemically modified at only Fc basis amino groups of the immunoglobulin.
Claim 35
Dependent Claim
27 words
The method of claim 32 wherein said method comprises exposing a mammalian subject to immunoglobulin that has been chemically modified at only lysine groups of the immunoglobulin.
Claim 36
Independent Claim
60 words
A method of producing chemically modified immunoglobulin having a Fab region and an Fc region with improved immunoreactivity comprising the steps of: determining the individual isoelectric points of the Fc and Fab fragments of the immunoglobulin; and performing a chemical modification of Fc region amino groups of said immunoglobulin at a pH within the range of the two isoelectric points.
Claim 37
Independent Claim
60 words
A method of producing chemically modified immunoglobulin having a Fab region and an Fc region with improved immunoreactivity comprising the steps of: determining the individual isoelectric points of the Fc and Fab fragments of the immunoglobulin; and performing a chemical modification of Fc region amino groups of said immunoglobulin at a pH within the range of the two isoelectric points.
Claim 38
Dependent Claim
33 words
The method of claim 34 wherein said method comprises performing a chemical modification of Fc region basic amino groups of said immunoglobulin at a pH within the range of the two isoelectric points.
Claim 39
Dependent Claim
32 words
The method of claim 35 wherein said method comprises performing a chemical modification of Fc region lysine groups of the immunoglobulin at a pH within the range of the two isoelectric points.
Claim 40
Independent Claim
64 words
A method of enhancing the sensitivity of an immunoglobulin having a Fab region and an Fc region for use in diagnostic testing using a target, said method comprising exposing the target to an immunoglobulin that has been chemically modified at only Fc region amino groups of the immunoglobulin at a pH between the isoelectric points of the Fab and Fc fragments of the immunoglobulin.
Claim 41
Independent Claim
64 words
A method of enhancing the sensitivity of an immunoglobulin having a Fab region and an Fc region for use in diagnostic testing using a target, said method comprising exposing the target to an immunoglobulin that has been chemically modified at only Fc region amino groups of the immunoglobulin at a pH between the isoelectric points of the Fab and Fc fragments of the immunoglobulin.
Claim 42
Dependent Claim
29 words
The method of claim 37 wherein said method comprises exposing the target to an immunoglobulin that has been chemically modified at Fc region basic amino groups of the immunoglobulin.
Claim 43
Dependent Claim
28 words
The method of claim 38 wherein said method comprises exposing the target to an immunoglobulin that has been chemically modified at Fc region lysine groups of the immunoglobulin.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1996-05-03 | 1996-11-02 | 1997-05-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-05-03 | 2000-11-02 | 2001-05-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-05-03 | 2004-11-02 | 2005-05-04 | $7700.00 | Window Closed / Lapsed |