Anti-NGF compositions and use thereof
View Patent ↗The present invention is directed to antibodies and fragments thereof having binding specificity for NGF. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the V H , V L and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-NGF antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-NGF antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-NGF antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with NGF.
1. A humanized or chimeric anti-human NGF antibody or fragment thereof that specifically binds to human nerve growth factor (human NGF) comprising (i) a variable light (V L ) chain polypeptide comprising a CDR1 sequence of SEQ ID NO:25, a CDR2 sequence of SEQ ID NO:26, and a CDR3 sequence of SEQ ID NO:27, and (ii) a variable heavy (V H ) chain polypeptide comprising a CDR1 sequence of SEQ ID NO:28, a CDR2 sequence of SEQ ID NO:29, and a CDR3 sequence of SEQ ID NO:30.
2. The antibody fragment of claim 1 , wherein said fragment is selected from a Fab fragment, a Fab′ fragment, and a F(ab′) 2 fragment.
3. The antibody fragment of claim 2 , wherein said antibody fragment is a Fab1 fragment comprising the amino acid sequence of SEQ ID NOs: 23, and 21 or 22 or a Fab2 fragment comprising the amino acid sequence of SEQ ID NOs: 24, and 21 or 22.
4. A composition containing an anti-NGF Fab1 or Fab2 fragment of claim 3 .
5. The composition of claim 4 , wherein said composition is a pharmaceutical composition comprising a pharmaceutical excipient.
6. The antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment comprises (i) a V H chain polypeptide identical to the amino acid sequence of SEQ ID NO:23 or SEQ ID NO:24, and (ii) a V L chain polypeptide identical to the amino acid sequence of SEQ ID NO:21 or SEQ ID NO:22.
7. The antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment thereof is aglycosylated.
8. The antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment thereof comprises an F c region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.
9. The antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment thereof is humanized.
10. The antibody or antibody fragment of claim 9 , wherein the antibody or antibody fragment comprises a human F c region.
11. The antibody or antibody fragment of claim 10 , wherein the human F c region is selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.
12. The antibody or antibody fragment of claim 1 , wherein said antibody is directly or indirectly attached to a detectable label or a therapeutic agent.
13. The antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment further comprises an effector moiety.
14. The antibody or antibody fragment of claim 13 , wherein the effector moiety is a detectable moiety or a functional moiety.
15. The antibody or antibody fragment of claim 14 , wherein said detectable moiety is a fluorescent dye, an enzyme, a substrate, a bioluminescent material, a radioactive material, or a chemiluminescent material.
16. The antibody or antibody fragment of claim 14 , wherein said functional moiety is streptavidin, avidin, biotin, a cytotoxin, a cytotoxic agent, or a radioactive material.
17. A pharmaceutical or diagnostic composition comprising the antibody or antibody fragment of claim 1 and a pharmaceutically acceptable excipient.