Humanized antibodies against human interferon-alpha
The present invention provides humanized anti-human IFN-α monoclonal antibodies useful for therapeutic applications in humans. Preferred antibodies are humanized versions of murine antibodies ACO-1 and ACO-2, as well as variants thereof.
1. An isolated antibody comprising at least one light chain that comprises the CDRs:
VL1 having the amino acid sequence of SEQ ID NO:33;
VL2 having the amino acid sequence of SEQ ID NO:19; and
VL3 having the amino acid sequence of SEQ ID NO:20; and
at least one heavy chain that comprises the CDRs:
VH1 having the amino acid sequence of SEQ ID NO:15;
VH2 having the amino acid sequence of SEQ ID NO:21; and
VH3 having the amino acid sequence of SEQ ID NO:17.
2. The antibody of claim 1 , wherein said heavy chain further has the amino acid residue R adjacent to the N-terminus of said VH1, as described by SEQ ID NO:34.
3. The antibody of claim 2 , wherein said heavy chain further has the amino acid residues V and R adjacent to the N-terminus of said VH3, as described by SEQ ID NO:35.
4. The antibody of claim 1 that is an IgG4 isotype antibody.
5. The antibody of claim 2 that is an IgG4 isotype antibody.
6. The antibody of claim 3 that is an IgG4 isotype antibody.
7. The antibody of claim 1 which is an antibody fragment, wherein the antibody fragment specifically neutralizes a bioactivity of IFN-α protein subtypes A, 2, B2, C, F, G, H2, I, J1, K, 4a, 4b and WA, but does not significantly neutralize said bioactivity of IFN-α protein subtype D, wherein said bioactivity is activation of the MxA promoter or antiviral activity.
8. The antibody of claim 2 which is an antibody fragment, wherein the antibody fragment specifically neutralizes a bioactivity of IFN-α protein subtypes A, 2, B2, C, F, G, H2, I, J1, K, 4a, 4b and WA, but does not significantly neutralize said bioactivity of IFN-α protein subtype D, wherein said bioactivity is activation of the MxA promoter or antiviral activity.
9. The antibody of claim 3 which is an antibody fragment, wherein the antibody fragment specifically neutralizes a bioactivity of IFN-α protein subtypes A, 2, B2, C, F, G, H2, I, J1, K, 4a, 4b and WA, but does not significantly neutralize said bioactivity of IFN-α protein subtype D, wherein said bioactivity is activation of the MxA promoter or antiviral activity.
10. A pharmaceutical composition comprising the antibody of claim 1 and a carrier.
11. A pharmaceutical composition comprising the antibody of claim 2 and a carrier.
12. A pharmaceutical composition comprising the antibody of claim 3 and a carrier.