Modulation of antibody specificity by tailoring the affinity to cognate antigens
First Claim
1. A method of tailoring the specificity of a pan-specific antibody that specifically binds at least two members within a receptor tyrosine kinase (RTK) family, said method comprising randomizing each amino acid of the CDRs of said pan-specific antibody;
- generating a library comprising said randomized CDRs; and
screening said library for clones with altered affinity for a desired receptor(s).
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Abstract
The present invention relates to methods and compositions designed for the treatment, management, prevention and/or amelioration of various disorders associated with aberrant expression and/or activity of one or more Eph receptor tyrosine kinase family members and/or one or more Eph receptor ligands, particularly the Ephrins. In particular, the invention provides methods for the treatment, management, prevention and/or amelioration of a disorder associated with aberrant expression and/or activity(ies) of one or more Eph receptors and/or one or more Ephrins, the method comprising administering to a subject in need thereof an effective amount of one or more Eph/Ephrin Modulators. The present invention further relates to methods of modulating antibody specificity by tailoring the affinity to cognate antigens.
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Citations
64 Claims
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1. A method of tailoring the specificity of a pan-specific antibody that specifically binds at least two members within a receptor tyrosine kinase (RTK) family, said method comprising randomizing each amino acid of the CDRs of said pan-specific antibody;
- generating a library comprising said randomized CDRs; and
screening said library for clones with altered affinity for a desired receptor(s). - View Dependent Claims (2, 3, 4, 5, 6)
- generating a library comprising said randomized CDRs; and
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7. An antibody that specifically binds the Eph receptor epitope to which monoclonal antibody GEA44 binds.
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8. An antibody that has been tailored to specifically bind desired combinations of members of the Eph family of receptors, said binding being represented by the following formulas:
- EphA(x)+[EphB(y)](n2);
EphA(x)+[EphA(x)](n1);
EphB(y)+[EphB(y)](n2);
EphB(y)+[EphA(x)](n1) or [EphA(x)](n1)+[EphB(y)](n2), wherein (x) is 1, 2, 3, 4, 5, 6, 7, 8, or 10, (y) is 1, 3, 4, 5 or 6, (n1) is a multiple of 0-8, and (n2) is a multiple of 0-5. - View Dependent Claims (9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48)
- EphA(x)+[EphB(y)](n2);
- 49. A method for treating or preventing a disorder associated with aberrant Eph receptor or Ephrin expression in a subject comprising administering to the subject in need of said treating or preventing an effective amount of Eph/Ephrin Modulator.
Specification