Compositions and methods for generating chimeric heteromultimers
First Claim
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1. A non-single-chain antigen-binding unit comprising:
- (a) a light (L) chain polypeptide comprising a light (L) chain variable region fused in-frame to a first heterodimerization polypeptide;
(b) a heavy (H) chain polypeptide comprising a heavy (H) chain variable region fused in-frame to a second heterodimerization polypeptide;
wherein the L chain and the H chain polypeptides dimerize via pairwise affinity of the first and second heterodimerization polypeptides; and
wherein at least one of the heterodimerization polypeptides is essentially incapable of fanning a homodimer under physiological buffer conditions and/or at physiological body temperatures.
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Abstract
The present invention provides a technique for specific assembly of monomeric polypeptides to form a heteromultimer. This technique is particularly useful for generating a genetically diverse repertoire of heteromultimers such as antigen-binding units. The invention also provides both non-single-chain and single-chain antigen-binding units that are assembled by the technique described herein. The present invention also provides recombinant polynucleotides, vectors, host cells, and kits for producing the subject antigen-binding units. Further provided by the invention are methods of using the subject antigen-binding units.
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Citations
38 Claims
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1. A non-single-chain antigen-binding unit comprising:
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(a) a light (L) chain polypeptide comprising a light (L) chain variable region fused in-frame to a first heterodimerization polypeptide;
(b) a heavy (H) chain polypeptide comprising a heavy (H) chain variable region fused in-frame to a second heterodimerization polypeptide;
wherein the L chain and the H chain polypeptides dimerize via pairwise affinity of the first and second heterodimerization polypeptides; and
wherein at least one of the heterodimerization polypeptides is essentially incapable of fanning a homodimer under physiological buffer conditions and/or at physiological body temperatures.- View Dependent Claims (2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 31, 32, 33, 34, 35, 36, 37, 38)
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3. A non-single-chain antigen-binding unit comprising:
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(a) a light (L) chain polypeptide comprising a light (L) chain variable region fused in-frame to a first heterodimerization polypeptide;
(b) a heavy (H) chain polypeptide comprising a heavy (H) chain variable region fused in-frame to a second heterodimerization polypeptide;
wherein the L chain and the H chain polypeptides dimerize via pairwise affinity of the first and second heterodimerization polypeptides, said first and second heterodimerization polypeptides comprising polypeptides from heterodimeric receptors that mediate heterodimerization of said receptors.
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20. A single-chain antigen-binding unit comprising a light chain variable region (VL) and a heavy chain variable region (VH) connected by a first and a second heterodimerization polypeptide spanning the distance between the C-terminus of one of the region to the N-terminus of the other region in the configuration of VH—
- (first heterodimerization polypeptide)-(second heterodimerization polypeptide)—
VL, or VL—
(first heterodimerization polypetide)-(second heterodimerization polypetide)—
VH, wherein the two regions form an intra-molecular dimer via pairwise affinity of the first and second heterodimerization polypeptides; and
wherein at least one of the heterodimerization polypeptides is essentially incapable of forming a homodimer under physiological buffer conditions and/or at physiological body temperatures. - View Dependent Claims (21, 23, 24, 25, 26, 27, 28, 29, 30)
- (first heterodimerization polypeptide)-(second heterodimerization polypeptide)—
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22. A single-chain antigen-binding unit comprising a light chain variable region (VL) and a heavy chain variable region (VH) connected by a first and a second heterodimerization polypeptide spanning the distance between the C-terminus of one of the region to the N-terminus of the other region in the configuration of VH—
- (first heterodimerization polypetide)-(second heterodimerization polypeptide)—
VL, or VL—
(first heterodimerization polypeptide)-(second heterodimerization polypetide)—
VH, wherein the two regions form an intra-molecular dimer via pairwise affinity of the first and second heterodimerization polypeptides, said first and second heterodimerization polypeptides comprising polypeptides from heterodimeric receptors that mediate heterodimerization of the receptors.
- (first heterodimerization polypetide)-(second heterodimerization polypeptide)—
Specification