JP2011523359A5 - - Google Patents

Claims (28)

An isolated anti-PirB / LILRB antibody that essentially binds to the same epitope on human PirB (LILRB) as an antibody selected from the group consisting of YW259.2, YW259.9, and YW259.12 , comprising antibody YW259 .2 includes the heavy chain sequence of SEQ ID NO: 4 or 11 and the light chain sequence of SEQ ID NO: 7, YW259.9 includes the heavy chain sequence of SEQ ID NO: 5 or 12, and the light chain sequence of SEQ ID NO: 7, and YW259.12 Or an antigen-binding fragment thereof, comprising a heavy chain sequence of SEQ ID NO: 6 or 13 and a light chain sequence of SEQ ID NO: 7 . An isolated anti-PirB / LILRB antibody that competes for binding to human PirB (LILRB) with an antibody selected from the group consisting of YW259.2, YW259.9 and YW259.12 , wherein antibody YW259.2 is a sequence YW259.9 includes the heavy chain sequence of SEQ ID NO: 5 or 12, and the light chain sequence of SEQ ID NO: 7, and YW259.12 includes SEQ ID NO: 6. Or an antibody or antigen-binding fragment thereof comprising the heavy chain sequence of 13 and the light chain sequence of SEQ ID NO: 7 . Includes all three hypervariable region sequences of heavy chain sequences selected from the group consisting of the polypeptide sequences of SEQ ID NO: 4, SEQ ID NO: 11, Y SEQ ID NO: 5, SEQ ID NO: 12, SEQ ID NO: 6 or SEQ ID NO: 13. An isolated anti-PirB / LILRB antibody, or antigen-binding fragment thereof, comprising a heavy chain and / or a light chain comprising all three hypervariable region sequences of the polypeptide sequence of SEQ ID NO: 7 or SEQ ID NO: 15 . Three of the hypervariable region sequences of the heavy chain sequence wherein the antibody is selected from the group consisting of the polypeptide sequences of SEQ ID NO: 4, SEQ ID NO: 11, Y SEQ ID NO: 5, SEQ ID NO: 12, SEQ ID NO: 6 or SEQ ID NO: 13. 4. The antibody or antigen-binding fragment thereof of claim 3 , comprising a light chain comprising all and all three of the hypervariable region sequences of the polypeptide sequence of SEQ ID NO: 7 or SEQ ID NO: 15 . YW259.2, wherein the antibody comprises the heavy chain sequence of SEQ ID NO: 4 and the light chain sequence of SEQ ID NO: 7, YW259.9 comprising the heavy chain sequence of SEQ ID NO: 5 and the light chain sequence of SEQ ID NO: 7, and the heavy of SEQ ID NO: 6 The antibody or antigen-binding fragment thereof according to claim 3, selected from the group consisting of an antibody of YW259.12 comprising a chain sequence and the light chain sequence of SEQ ID NO: 7. 4. The antibody or antigen-binding fragment thereof according to claim 3 , wherein the full-length IgG form of the antibody specifically binds to human PirB (LILRB) with a binding affinity of 5 nM or more , or 1 nM or more . The antibody or antigen-binding fragment thereof according to any one of claims 1 to 6 , which promotes axonal regeneration or CNS neuron regeneration . The antibody or antigen-binding fragment thereof according to any one of claims 1-6 , which at least partially rescues neurite outgrowth inhibition by Nogo 66 and myelin. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 8 , wherein the antibody is a monoclonal antibody. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 9 , wherein the antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, an affinity matured antibody, a human antibody, and a bispecific antibody. . The antibody or antigen-binding fragment thereof according to any one of claims 1 to 10 , wherein the antibody is an immunoconjugate. A polynucleotide encoding the antibody or antigen-binding fragment thereof according to any one of claims 1 to 10 , or the heavy or light chain thereof. A vector comprising the polynucleotide of claim 12 . 14. The vector of claim 13 , wherein the vector is an expression vector. A host cell comprising the vector of claim 13 or 14 . 16. The host cell of claim 15 , wherein the host cell is a prokaryotic , eukaryotic or mammalian host cell. A method for producing an anti-PirB / LILRB antibody or antigen-binding fragment thereof , comprising: (a) expressing the vector of claim 14 in a suitable host cell; and (b) recovering the antibody or antigen-binding fragment. Including methods. A composition comprising the anti-PirB / LILRB antibody or antigen-binding fragment according to any one of claims 1-11 as a first medicament , and a pharmaceutically acceptable excipient , optionally A composition further comprising two medicaments . The composition of claim 18 , wherein the second medicament is an NgR inhibitor. 20. The composition of claim 19 , wherein the NgR inhibitor is an anti-NgR antibody. A kit comprising the anti-PirB / LILRB antibody or antigen-binding fragment according to any one of claims 1-11 . Use of an anti-PirB / LILRB antibody or antigen-binding fragment according to any one of claims 1-11 in the manufacture of a medicament for promoting axonal regeneration in a human patient . 23. Use according to claim 22 , wherein neuronal survival is enhanced or neuronal elongation is induced . Use of an anti-PirB / LILRB antibody or antigen-binding fragment according to any one of claims 1-11 in the manufacture of a medicament for treating a neurodegenerative disease in a human patient . Use according to claim 24, the neurodegenerative disorder characterized by physical damage to the central nervous system. 26. The use according to claim 25, wherein the physical damage to the central nervous system is brain damage associated with stroke. Neurodegenerative diseases include trigeminal neuralgia, glossopharyngeal neuralgia, bell palsy, myasthenia gravis, muscular dystrophy, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), progressive muscular atrophy, progressive Peripheral nerve injury caused by medullary hereditary muscular atrophy, physical injury (eg burns, wounds) or disease states such as diabetes, renal failure or cancer and the toxic effects of chemotherapeutic agents used to treat AIDS, hereditary , Ruptured or prolapsed invertebrate disc syndrome, cervical spondylosis, plexus disease, thoracic outlet destruction syndrome, peripheral neuropathy such as lead, dapsone, tick, porphyria, Guillain-Barre syndrome, Alzheimer's disease, Huntington's disease And use according to claim 24, selected from the group consisting of those caused by Parkinson's disease. An anti-idiotype antibody that specifically binds to the anti-PirB / LILRB antibody or antigen-binding fragment according to any one of claims 1 to 11 , or an antigen-binding fragment thereof .