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US 8,945,550 B2Granted
Antibodies and methods for making and using them
AssigneeMMRGlobal, Inc.
InventorsGerhard Frey, Bruce E. Kimmel, Abraham Anderson
Life of this patent
Estimating the term…
Abstract
The invention provides antibodies, including chimeric human antibodies, recombinant antibodies, synthetic anti-bodies, and the nucleic acids encoding them, and methods for making and using these immunoglobulins. The invention provides recombinant and synthetic polypeptide and nucleic acid embodiments of these polypeptides and/or antibodies. The invention also provides polypeptides comprising, or consisting of, consensus human framework regions, or “Independently Consensused Frameworks (ICFs)”, nucleic acids encoding them, and libraries and kits comprising these ICFs and/or antibodies of the invention, individually and in combinatorial libraries and combinations.
Claims4
A method for treating or ameliorating a B-cell mediated disease comprising:
- (a) providing a composition comprising an antibody or an antigen binding fragment thereof comprising at least one of the following combinations:
- (1) light chain BD22088 (SEQ ID NO:229) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (2) light chain BD22090 (SEQ ID NO:234) and heavy chain BD20337 (SEQ ID NO:148);
- (3) light chain BD22095 (SEQ ID NO:244) and heavy chain BD20337 (SEQ ID NO:148);
- (4) light chain BD22091 (SEQ ID NO:242) and heavy chain BD20337 (SEQ ID NO:148);
- (5) light chain BD22108 (SEQ ID NO:230) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (6) light chain BD22092 (SEQ ID NO:235) and heavy chain BD20338 (SEQ ID NO:149);
- (7) light chain BD22094 (SEQ ID NO:231) and heavy chain BD20337 (SEQ ID NO:148);
- (8) light chain BD22096 (SEQ ID NO:241) and heavy chain BD20337 (SEQ ID NO:148);
- (9) light chain BD22092 (SEQ ID NO:235) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (10 light chain BD22102 (SEQ ID NO:248) and heavy chain BD20337 (SEQ ID NO:148);
- (11) light chain BD22104 (SEQ ID NO:239) and heavy chain BD20337 (SEQ ID NO:148);
- (12) light chain BD22103 (SEQ ID NO:228) and heavy chain BD20337 (SEQ ID NO:
- 148);
- or
- (13) light chain BD22105 (SEQ ID NO:237) and heavy chain BD20337 (SEQ ID NO:
- 148);
- and
- wherein the at least a portion of a light chain, the at least a portion of the heavy chain, or both are derived at least in part from sequences made by the method comprising:
- (1) providing an Independently Consensused Framework I (ICFI) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region I (KFI) domain, wherein the plurality of amino acid sequences are translated from a germline sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- (2) providing at least a portion of a complementarity determining region 1 (CDR1) derived from the variable region of a 1FS antibody;
- (3) providing an Independently Consensused Framework 2 (ICF2) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region 2 (KF2) domain, wherein the plurality of amino acid sequences translated from a germline sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- (4) providing at least a portion of a complementarity determining region 2 (CDR2) derived from the variable region of a IFS antibody;
- (5) providing an Independently Consensused Framework 3 (ICF3) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region 3 (KF3) domain, wherein the plurality of amino acid sequences are translated from a germline sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- (6) providing at least a portion of a complementarity determining region 3 (CDR3) derived from the variable region of a IFS antibody;
- and
- (7) optionally providing an Independently Consensused Framework 4 (ICF4) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region 4 (KF4) domain, wherein the plurality of amino acid sequences are translated from a germline sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- wherein at least one rCF is derived from a genomic nucleic acid sequence,
- (8) joining, in a 5′-to-3′ orientation, nucleic acids encoding the ICF1-CDR1-ICF2-CDR2-ICF3-CDR3 and optionally ICF4 domains;
- and
- (b) administering an amount of said antibody or antigen binding fragment thereof to an individual in need thereof sufficient to ameliorate said B-cell mediated disease in said individual.
31 more elements
A method for suppressing or abrogating a B-cell mediated immune response comprising:
- (a) providing an antibody or antigen binding fragment thereof comprising at least one of the following combinations:
- (1) light chain BD22088 (SEQ ID NO:229) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (2) light chain BD22090 (SEQ ID NO:234) and heavy chain BD20337 (SEQ ID NO:148);
- (3) light chain BD22095 (SEQ ID NO:244) and heavy chain BD20337 (SEQ ID NO:148);
- (4) light chain BD22091 (SEQ ID NO:242) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (5) light chain BD22108 (SEQ ID NO:230) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (6) light chain BD22092 (SEQ ID NO:235) and heavy chain BD20338 (SEQ ID NO:149);
- (7) light chain BD22094 (SEQ ID NO:231) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (8) light chain BD22096 (SEQ ID NO:241) and heavy chain BD20337 (SEQ ID NO:148);
- (9) light chain BD22092 (SEQ ID NO:235) and heavy chain BD20337 (SEQ ID NO:148);
- (10 light chain BD22102 (SEQ ID NO:248) and heavy chain BD20337 (SEQ ID NO:148);
- (11) light chain BD22104 (SEQ ID NO:239) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (12) light chain BD22103 (SEQ ID NO:228) and heavy chain BD20337 (SEQ ID NO:148);
- or
- (13) light chain BD22105 (SEQ ID NO:237) and heavy chain BD20337 (SEQ ID NO:148);
- and
- wherein the at least a portion of a light chain, the at least a portion of the heavy chain, or both are derived at least in part from sequences made by the method comprising:
- (1) providing an Independently Consensused Framework I (ICFI) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region I (KFI) domain, wherein the plurality of amino acid sequences are translated from a germline sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- (2) providing at least a portion of a complementarity determining region 1 (CDR 1) derived from the variable region of a IFS antibody;
- (3) providing an Independently Consensused Framework 2 (ICF2) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region 2 (KF2) domain, wherein the plurality of amino acid sequences translated from a germ line sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- (4) providing at least a portion of a complementarity determining region 2 (CDR2) derived from the variable region of a IFS antibody;
- (5) providing an Independently Consensused Framework 3 (ICF3) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region 3 (KF3) domain, wherein the plurality of amino acid sequences are translated from a germline sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- (6) providing at least a portion of a complementarity determining region 3 (CDR3) derived from the variable region of a IFS antibody;
- and
- (7) optionally providing an Independently Consensused Framework 4 (ICF4) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region 4 (KF4) domain, wherein the plurality of amino acid sequences are translated from a germ line sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- wherein at least one rCF is derived from a genomic nucleic acid sequence,
- (8) joining, in a 5′-to-3′ orientation, nucleic acids encoding the ICF1-CDR1-ICF2-CDR2-ICF3-CDR3 and optionally ICF4 domains;
- and
- (b) administering an amount of said antibody or antigen binding fragment thereof to an individual in need thereof sufficient to suppress or abrogate said B-cell mediated immune response in said individual.
31 more elements
A method of treating B-cell lymphoma comprising:
- (a) providing an antibody or antigen binding fragment thereof comprising at least one of the following combinations:
- (1) light chain BD22088 (SEQ ID NO:229) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (2) light chain BD22090 (SEQ ID NO:234) and heavy chain BD20337 (SEQ ID NO:148);
- (3) light chain BD22095 (SEQ ID NO:244) and heavy chain BD20337 (SEQ ID NO:148);
- (4) light chain BD22091 (SEQ ID NO:242) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (5) light chain BD22108 (SEQ ID NO:230) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (6) light chain BD22092 (SEQ ID NO:235) and heavy chain BD20338 (SEQ ID NO:149);
- (7) light chain BD22094 (SEQ ID NO:231) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (8) light chain BD22096 (SEQ ID NO:241) and heavy chain BD20337 (SEQ ID NO:148);
- (9) light chain BD22092 (SEQ ID NO:235) and heavy chain BD20337 (SEQ ID NO:148);
- (10 light chain BD22102 (SEQ ID NO:248) and heavy chain BD20337 (SEQ ID NO:148);
- (11) light chain BD22104 (SEQ ID NO:239) and heavy chain BD20337 (SEQ ID NO:
- 148);
- (12) light chain BD22103 (SEQ ID NO:228) and heavy chain BD20337 (SEQ ID NO:148);
- or
- (13) light chain BD22105 (SEQ ID NO:237) and heavy chain BD20337 (SEQ ID NO:148);
- and
- wherein the at least a portion of a light chain, the at least a portion of the heavy chain, or both are derived at least in part from sequences made by the method comprising:
- (1) providing an Independently Consensused Framework I (ICFI) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region I (KFI) domain, wherein the plurality of amino acid sequences are translated from a germline sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- (2) providing at least a portion of a complementarity determining region 1 (CDR 1) derived from the variable region of a IFS antibody;
- (3) providing an Independently Consensused Framework 2 (ICF2) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region 2 (KF2) domain, wherein the plurality of amino acid sequences translated from a germ line sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- (4) providing at least a portion of a complementarity determining region 2 (CDR2) derived from the variable region of a IFS antibody;
- (5) providing an Independently Consensused Framework 3 (ICF3) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region 3 (KF3) domain, wherein the plurality of amino acid sequences are translated from a germline sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- (6) providing at least a portion of a complementarity determining region 3 (CDR3) derived from the variable region of a IFS antibody;
- and
- (7) optionally providing an Independently Consensused Framework 4 (ICF4) domain, comprising an amino acid consensus sequence derived from a plurality of amino acid sequences each comprising amino acids derived from at least a portion of a Kabat framework region 4 (KF4) domain, wherein the plurality of amino acid sequences are translated from a germ line sequence of an immunoglobulin variable region gene or obtained from a mature immunoglobulin;
- wherein at least one rCF is derived from a genomic nucleic acid sequence,
- (8) joining, in a 5′-to-3′ orientation, nucleic acids encoding the ICF1-CDR1-ICF2-CDR2-ICF3-CDR3 and optionally ICF4 domains;
- and
- (b) administering an amount of said antibody or fragment thereof to an individual in need thereof sufficient to treat said B-cell lymphoma in said patient.
31 more elements
Dependencies are inferred from the claim text.