Anti- alphavbeta3 recombinant human antibodies, nucleic acids encoding same and methods of use
AssigneeApplied Molecular Evolution, Inc.
InventorsWilliam D. Huse, Herren Wu
Life of this patent
Estimating the term…
Abstract
The invention provides enhanced LM609 grafted antibodies exhibiting selective binding affinity to αVβ3, or a functional fragment thereof. The invention also provides nucleic acid molecules encoding the enhanced LM609 grafted antibodies. Additionally provided are methods of inhibiting a function of αVβ3 by contacting αVβ3 with an enhanced LM609 grafted antibody.
Claims86
An enhanced LM609 grafted antibody exhibiting selective binding affinity to αVβ3, or a functional fragment thereof, comprising a CDR selected from the group consisting of a VH CDR2 referenced as SEQ ID NO:104;
- a VH CDR3 referenced as SEQ ID NO:106;
- and a VL CDR1 referenced as SEQ ID NO:110.
An enhanced LM609 grafted antibody exhibiting selective binding affinity to αVβ3 or a functional fragment thereof, comprising the VH CDR1 referenced as SEQ ID NO:34;
- the V™, CDR2 referenced as SEQ ID NO:102;
- the VH CDR3 referenced as SEQ ID NO:106;
- the VL CDR1 referenced as SEQ ID NO:108;
- the VL CDR2 referenced as SEQ ID NO:112;
- and the VL CDR3 referenced as SEQ ID NO:90.
An enhanced LM609 grafted antibody exhibiting selective binding affinity to αVβ3, or a functional fragment thereof, comprising the VH CDR1 referenced as SEQ ID NO:34;
- the VH CDR2 referenced as SEQ ID NO:102;
- the VH CDR3 referenced as SEQ ID NO:106;
- the VL CDR1 referenced as SEQ ID NO:110;
- the VL CDR2 referenced as SEQ ID NO:112;
- and the VL CDR3 referenced as SEQ ID NO:90.
An enhanced LM609 grafted antibody exhibiting selective binding affinity to αVβ3, or a functional fragment thereof, comprising the VH CDR1 referenced as SEQ ID NO:34;
- the VH CDR2 referenced as SEQ ID NO:104;
- the VH CDR3 referenced as SEQ ID NO:106;
- the VL CDR1 referenced as SEQ ID NO:110;
- the VL CDR2 referenced as SEQ ID NO:112;
- and the VL CDR3 referenced as SEQ ID NO:90.
An antibody, or a functional fragment thereof, comprising a CDR selected from the group consisting of a VH CDR2 referenced as SEQ ID NO:104;
- a VH CDR3 referenced as SEQ ID NO:106;
- and a VL CDR1 referenced as SEQ ID NO:110, and exhibiting enhanced binding affinity to αVβ3 compared to LM609.
An antibody, or functional fragment thereof, comprising the VH CDR1 referenced as SEQ ID NO:34;
- a VH CDR2 referenced as SEQ ID NO:102;
- a VH CDR3 referenced as SEQ ID NO:106;
- a VL CDR1 referenced as SEQ ID NO:108;
- a VL CDR2 referenced as SEQ ID NO:112;
- and a VL CDR3 referenced as SEQ ID NO:90, and exhibiting enhanced binding activity to αVβ3 compared to LM609.
An antibody, or a functional fragment thereof, comprising a VH CDR1 referenced as SEQ ID NO:34;
- a VH CDR2 referenced as SEQ ID NO:102;
- a VH CDR3 referenced as SEQ ID NO:106;
- a VL CDR1 referenced as SEQ ID NO:110;
- a VL CDR2 referenced as SEQ ID NO:112;
- and a VL CDR3 referenced as SEQ ID NO:90, and exhibiting enhanced binding activity to αVβ3 compared to LM609.
An antibody, or a functional fragment thereof, comprising a VH CDR1 referenced as SEQ ID NO:34;
- a VH CDR2 referenced as SEQ ID NO:104;
- a VH CDR3 referenced as SEQ ID NO:106;
- a VL CDR1 referenced as SEQ ID NO:110;
- a VL CDR2 referenced as SEQ ID NO:112;
- and a VL CDR3 referenced as SEQ ID NO:90, and exhibiting enhanced binding activity to αVβ3 compared to LM609.
A nucleic acid molecule having a nucleotide sequence selected from the group of nucleotide sequences consisting of SEQ ID NO:33, SEQ ID NO:89, SEQ ID NO:101;
- SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, and SEQ ID NO:111.
A method of inhibiting a function of αVβ3, comprising contacting αVβ3 with an antibody, or a functional fragment thereof, comprising a CDR selected from the group consisting of a VH CDR2 referenced as SEQ ID NO:104;
- a VH CDR3 referenced as SEQ ID NO:106;
- and a VL CDR1 referenced as SEQ ID NO:110, said antibody or functional fragment thereof having integrin αVβ3 binding activity, integrin αVβ3 binding specificity or integrin αVβ3-inhibitory activity.
A method of treating an αVβ3-mediated disease, comprising contacting αVβ3 with an antibody, or a functional fragment thereof, comprising a CDR selected from the group consisting of a VH CDR2 referenced as SEQ ID NO:104;
- a VH CDR3 referenced as SEQ ID NO:106;
- and a VL CDR1 referenced as SEQ ID NO:110, said antibody or functional fragment thereof having integrin αVβ3 binding activity, integrin αVβ3 binding specificity or integrin αVβ3-inhibitory activity.
A method of treating cancer, comprising contacting αVβ3 with an antibody, or a functional fragment thereof, comprising a CDR selected from the group consisting of a VH CDR2 referenced as SEQ ID NO:104;
- a VH CDR3 referenced as SEQ ID NO:106;
- and a VL CDR1 referenced as SEQ ID NO:110, said antibody or functional fragment thereof having integrin αVβ3 binding activity, integrin αVβ3 binding specificity or integrin αVβ3-inhibitory activity.
A method of treating a tumor expressing αVβ3, comprising contacting αVβ3 with an antibody, or a functional fragment thereof, comprising a CDR selected from the group consisting of a VH CDR2 referenced as SEQ ID NO:104;
- a VH CDR3 referenced as SEQ ID NO:106;
- and a VL CDR1 referenced as SEQ ID NO:110, said antibody or functional fragment thereof having integrin αVβ3 binding activity, integrin αVβ3 binding specificity or integrin αVβ3-inhibitory activity.
A method of treating an inflammatory disorder, comprising contacting αVβ3 with an antibody, or a functional fragment thereof, comprising a CDR selected from the group consisting of a VH CDR2 referenced as SEQ ID NO:104;
- a VH CDR3 referenced as SEQ ID NO:106;
- and a VL CDR1 referenced as SEQ ID NO:110, said antibody or functional fragment thereof having integrin αvβ3 binding activity, integrin αVβ3 binding specificity or integrin αVβ3-inhibitory activity.
A method of treating a pathological condition involving neovascularization, comprising contacting αVβ3 with an antibody, or a functional fragment thereof, comprising a CDR selected from the group consisting of a VH CDR2 referenced as SEQ ID NO:104;
- a VH CDR3 referenced as SEQ ID NO:106;
- and a VL CDR1 referenced as SEQ ID NO:110, said antibody or functional fragment thereof having integrin αVβ3 binding activity, integrin αVβ3 binding specificity or integrin αVβ3-inhibitory activity.
Dependencies are inferred from the claim text.