Humanized anti-nerve growth factor antibodies
View Patent ↗Method for the humanization of the VH and VL variable regions of an animal antibody of known sequence, humanized animal antibody obtainable according to the method, in particular anti-NGF and anti-TrkA humanized animal antibodies.
1. A humanized anti-NGF antibody comprising a VH region having the amino acid sequence set forth in SEQ ID NO: 17 and a VL region having the amino acid sequence set forth in SEQ ID NO: 18, or a fragment thereof which maintains NGF binding activity.
2. A humanized anti-NGF antibody or a fragment thereof which maintains binding activity to NGF, wherein the humanized anti-NGF antibody comprises,
(a) a VH region having a first CDR comprising the amino acid sequence GFSLTNNNVNW (SEQ ID NO: 41), a second CDR comprising the amino acid sequence GVWAGGATDYNSALKS (SEQ ID NO: 42), and a third CDR comprising the amino acid sequence DGGYSSSTLYAMDA (SEQ ID NO: 43); and
(b) a VL region having a first CDR comprising the amino acid sequence RASEDIYNALA (SEQ ID NO: 44), a second CDR comprising the amino acid sequence HT, and a third CDR sequence comprising the amino acid sequence QHYFHYPRT (SEQ ID NO: 45).
3. The humanized anti-NGF antibody of claim 2 , wherein the framework of the VH region is at least 85% or more identical to the framework of the VH region of SEQ ID NO: 19.
4. The humanized anti-NGF antibody of claim 2 , wherein the framework of the VH region is 90-95% or more identical to the framework of the VH region of SEQ ID NO: 19.
5. The humanized anti-NGF antibody of claim 2 , wherein the framework of the VL region is at least 85% or more identical to the framework of the VL region of SEQ ID NO: 20.
6. The humanized anti-NGF antibody of claim 2 , wherein the framework of the VL region is at least 90-95% or more identical to the framework of the VL region of SEQ ID NO: 20.
7. The humanized anti-NFG antibody of claim 2 , wherein the framework of the VH region is at least 85% or more identical to the framework of SEQ ID NO: 19, and the framework of the VL region is at least 85% or more identical to the framework of SEQ ID NO: 20.
8. The humanized anti-NFG antibody of claim 2 , wherein the framework of the VH region is 90-95% or more identical to the framework of SEQ ID NO: 19, the framework of the VL region is at least 90-95% or more identical to the framework of SEQ ID NO: 20.
9. The humanized anti-NGF antibody of claims 1 or 2 wherein the isotype of the antibody is IgG, IgM, IgA, IgD or IgE.
10. The humanized anti-NGF antibody of claims 1 or 2 , wherein the fragment thereof which maintains binding activity to NGF is an Fab fragment, an (Fab') 2 , an Fv fragment or an single chain Fv fragment (scFv).
11. A pharmaceutical composition comprising the humanized anti-NGF antibody of fragment thereof claims 1 or 2 .