Reducing immunogenicities of immunoglobulins by framework-patching
AssigneeSkytech Technology Limited
InventorShawn Leung
Life of this patent
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Abstract
A novel approach, named framework (FR)-patching, to re-engineer immunoglobulin so as to reduce the potential immunogenicity, when used in the intended species, in particular, humans, without significant alterations in the specificity and affinity of the resultant immunoglobulin is described.
Claims24
A re-engineered, or framework (FR)-patched immunoglobulin containing the heavy and/or light chain variable region sequences from a parent antibody, in which at least one of the compartmentalized framework sequences, defined as FR1, FR2, FR3 and FR4 are replaced, or patched by the corresponding framework sequences from the heavy and light chain immunoglobulin variable region of a different species, wherein said re-engineered immunoglobulin chain comprises framework sequences derived from at least two different sources of immunoglobulin chains, wherein said different immunoglobulin chains can be sourced from different immunoglobulins of the same species or from different immunoglobulins of different species, and such FR-patched immunoglobulin binds specifically to an antigen with affinity comparable to, or within 3-fold of, that of the parent immunoglobulin.
A re-engineered, or FR-patched immunoglobulin according to claim (1), in which the particular FR chosen for patching or replacing each corresponding FR in the parent immunoglobulin:
- a. exhibits the highest degree of homology, or at least 60%, to the corresponding parent FR;
- b. exhibits the highest degree of sequence homology to the corresponding parent FR, preferably 100%, or contains conservatively similar amino acids, such as, gly, ala;
- val, ile, leu;
- asp, glu;
- asn, gln;
- ser, thr;
- lys, arg;
- and phe, tyr, at the three amino acids immediately adjacent to the flanking CDR's;
- and
- c. contains identical, or conservatively similar amino acids (as listed in claim 4b) to the corresponding parent FR at positions known to be close to, or have interactions with the CDR's/antigen binding site, as evaluated by computer modeling, crystal structure, published information, or prior experience
Dependencies are inferred from the claim text.