Hybrid antibodies
AssigneeAlexion Pharmaceuticals, Inc.
InventorsRussell Rother, Dayang Wu
Life of this patent
Estimating the term…
Abstract
Hybrid antibodies and/or hybrid antibody fragments and methods of making them are provided. In one embodiment the hybrid antibodies and/or hybrid antibody fragments contain heavy and/or light variable regions that contain two or more framework regions derived from at least two antibodies. In another embodiment, at least two of the framework regions are classified in the same germline gene family. In one embodiment, at least two framework regions are classified in the same germline gene family member. The hybrid antibodies or hybrid antibody fragments may contain human framework regions and nonhuman CDRs.
Claims43
A method for producing a hybrid antibody or hybrid antibody fragment comprising:
- providing an initial antibody having specificity for a target;
- determining the sequence of a variable region of the initial antibody;
- and
- (i) selecting a first component of the variable region selected from the group consisting of FR1, FR2, FR3 and FR4;
- comparing the sequence of the first component to sequences contained in a reference database of antibody sequences or antibody fragment sequences from a target species;
- selecting a first framework sequence from an antibody in the database which is one of the top one hundred hits based on sequence homology to the first component;
- (ii) selecting a second component of the variable region which is different than the first component, the second component selected from the group consisting of FR1, FR2, FR3 and FR4;
- comparing the sequence of the second component to sequences contained in a reference database of antibody sequences or antibody fragment sequences from the target species;
- selecting a second framework sequence from the database which is one of the top one hundred hits based on sequence homology to the second component, wherein the first and second framework sequences selected in step (i) are from different antibodies;
- and
- (iii) operatively linking the selected framework sequences to the CDRs and unselected framework sequences of the initial antibody to produce a hybrid antibody or hybrid antibody fragment that has specificity for said target, wherein the framework sequences and CDRs are linked together in the following arrangement:
- FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4.
A hybrid antibody or hybrid antibody fragment comprising
- (a) complementarity determining regions (CDRs) of an initial antibody, wherein said initial antibody is specific for a target,
- (b) a first heavy chain framework region from a first antibody, and
- (c) a second heavy chain framework region from a second antibody,
- wherein the first and second heavy chain framework regions are selected from the group consisting of FR1, FR2 and FR3, and wherein the hybrid antibody or hybrid antibody fragment is specific for said target.
A hybrid antibody or hybrid antibody fragment comprising
- (a) CDRs of an initial antibody, wherein said initial antibody is specific for a target,
- (b) a first light chain framework region from a first antibody, and
- (c) a second light chain framework region from a second antibody,
- wherein the first and second light chain framework regions are selected from the group consisting of FR1, FR2 and FR3, and wherein the hybrid antibody or hybrid antibody fragment is specific for said target.
Dependencies are inferred from the claim text.