Humanized antibodies
AssigneeArgen-X N.V.
InventorsTorsten Dreier, Johannes Joseph Wilhelmus De Haard
Life of this patent
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Abstract
The invention relates to novel humanized antibodies derived from the conventional antibody repertoire of species in the family Camelidae.
Claims49
A chimeric antibody which specifically binds a target antigen, the chimeric antibody comprising a VH domain comprising HCDR1, HCDR2, and HCDR3 region amino acid sequences and a VL domain comprising LCDR1, LCDR2, and LCDR3 region amino acid sequences, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 region amino acid sequences are obtained from a conventional camelid antibody,
- wherein the conventional camelid antibody is a heterotetrameric IgG antibody composed of two identical light chains and two identical heavy chains, wherein the heavy chains comprise a camelid VH domain paired with a camelid VL domain of said light chains, wherein the camelid VL domain is a camelid Vλ domain with a sequence identity of 90% or more to a human Vλ domain germline sequence across the framework regions FR1, FR2, FR3 and FR4,
- wherein the VL domain amino acid sequence of the chimeric antibody is obtained by substituting one or more amino acid residues of the camelid Vλ domain at one or more positions selected from the group consisting of L1, L2, L3, L5, L7, L8, L9, L11, L14, L15, L17, L18, L19, L20, L38, L39, L40, L42, L44, L46, L47, L49, L58, L59, L60, L66, L67, L69, L70, L71, L72, L74, L76, L78, L80, L81, L84, L103, L104 and L108, according to Kabat, with amino acids that are found at the corresponding position in the human Vλ domain germline sequence,
- wherein the VH domain and the VL domain of the chimeric antibody are each fused to one or more IgG constant domains of a human antibody, and
- wherein the HCDR1 and HCDR2 or the LCDR1 and LCDR2 of the conventional camelid antibody exhibit a combination of canonical fold structures which is identical or substantially identical to a combination of canonical fold structures for HCDR1 and HCDR2 or LCDR1 and LCDR2 of a human antibody.
A chimeric antibody, which specifically binds a target antigen, the chimeric antibody comprising a VH domain comprising HCDR1, HCDR2, and HCDR3 region amino acid sequences and a VL domain comprising LCDR1, LCDR2, and LCDR3 region amino acid sequences, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 region amino acid sequences are obtained from a conventional camelid antibody,
- wherein the conventional camelid antibody is a heterotetrameric IgG antibody composed of two identical light chains and two identical heavy chains, wherein the heavy chains comprise a camelid VH domain paired with a camelid VL domain of said light chains, wherein the camelid VL domain is a camelid Vκ domain with a sequence identity of 90% or more to a human Vκ domain germline sequence across the framework regions FR1, FR2, FR3, and FR4,
- wherein the VL domain amino acid sequence of the chimeric antibody is obtained by substituting one or more amino acids of the camelid Vκ domain at one or more positions selected from the group consisting of K1, K2, K3, K4, K7, K9, K11, K12, K13, K14, K15, K18, K19, K36, K39, K42, K43, K45, K46, K58, K63, K68, K70, K77, K78, K79, K80, K83, K100, K103, K104 and K106, according to Kabat, with amino acids that are found at the corresponding position in the human Vκ domain germline sequence,
- wherein the VH domain and the VL domain of the chimeric antibody are each fused to one or more IgG constant domains of a human antibody, and
- wherein the HCDR1 and HCDR2 or the LCDR1 and LCDR2 of the conventional camelid antibody exhibit a combination of canonical fold structures which is identical or substantially identical to a combination of canonical fold structures for HCDR1 and HCDR2 or LCDR1 and LCDR2 of a human antibody.
Dependencies are inferred from the claim text.