COVALENT DIABODIES AND USES THEREOF
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Abstract
The present invention is directed to diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through non-peptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody-like functionality to engineered into the molecule.
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Citations
135 Claims
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1-113. -113. (canceled)
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114. A dual affinity retargeting reagent (DART), wherein said DART comprises a diabody molecule comprising a first polypeptide chain and a second polypeptide chain, wherein:
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(A) said first polypeptide chain comprises; (i) a domain (A) comprising a binding region of a light chain variable domain of a first immunoglobulin (VL1) specific for an epitope (1); (ii) a domain (B) comprising a binding region of a heavy chain variable domain of a second immunoglobulin (VH2) specific for an epitope (2); and (iii) a domain (C) comprising a light chain constant region (CL) domain or portion thereof; (B) said second polypeptide chain comprises; (i) a domain (D) comprising a binding region of a light chain variable domain of the second immunoglobulin (VL2) specific for said epitope (2); (ii) a domain (E) comprising a binding region of a heavy chain variable domain of the first immunoglobulin (VH1) specific for said epitope (1); (iii) a domain (F) comprising a heavy chain constant region 1 (CH1) domain or portion thereof, and (iv) a hinge region a heavy chain constant region 2 (CH2) and a heavy chain constant region 3 (CH3); wherein; said domains (A) and (B) do not associate with one another to form an epitope binding site; said domains (D) and (E) do not associate with one another to form an epitope binding site; said domains (A) and (E) associate to form a binding site that binds said epitope (1);
said domains (B) and (D) associate to form a binding site that binds said epitope (2); andsaid domains (C) and (F) are associated together via a disulfide bond to form a CH1 domain or a portion thereof. - View Dependent Claims (115, 116, 117, 118, 120, 121, 122, 123, 124, 125, 129, 132, 133, 134, 135)
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119. (canceled)
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126-128. -128. (canceled)
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130. A dual affinity retargeting reagent (“
- DART”
), said reagent being composed on a plurality of polypeptide chains and being capable of simultaneously binding to two, three or more epitopes. - View Dependent Claims (131)
- DART”
Specification