B-cell reduction using CD37-specific and CD20-specific binding molecules
First Claim
1. A method for treating a disease or disorder associated with aberrant B-cell activity, the method comprising administering to a subject in need thereof an effective amount of a humanized or chimeric CD37-specific binding molecule derived from G28-1 and comprising a binding domain and immunoglobulin CH2 and CH3 domains, wherein the binding domain comprises a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 61;
a light chain CDR2 comprising the amino acid sequence of SEQ ID NO;
64;
a light chain CDR3 comprising the amino acid sequence of SEQ ID NO;
66;
a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO;
63;
a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO;
65; and
a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO;
67 or 68;
wherein said CD37-specific binding molecule specifically binds human CD37 on the surface of a B-cell in the subject.
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Abstract
The present invention generally provides methods for B-cell reduction in an individual using CD37-specific binding molecules. In particular, the invention provides methods for B-cell reduction using CD37-specific binding molecules alone, or a combination of CD37-specific binding molecules and CD20-specific binding molecules, in some instances a synergistic combination. The invention further provides materials and methods for treatment of diseases involving aberrant B-cell activity. In addition, the invention provides humanized CD37-specific binding molecules.
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Citations
8 Claims
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1. A method for treating a disease or disorder associated with aberrant B-cell activity, the method comprising administering to a subject in need thereof an effective amount of a humanized or chimeric CD37-specific binding molecule derived from G28-1 and comprising a binding domain and immunoglobulin CH2 and CH3 domains, wherein the binding domain comprises a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 61;
a light chain CDR2 comprising the amino acid sequence of SEQ ID NO;
64;
a light chain CDR3 comprising the amino acid sequence of SEQ ID NO;
66;
a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO;
63;
a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO;
65; and
a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO;
67 or 68;wherein said CD37-specific binding molecule specifically binds human CD37 on the surface of a B-cell in the subject. - View Dependent Claims (2, 3, 4, 8)
- 61;
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5. A method of reducing B cell tumor volume in a subject in need thereof, the method comprising administering an effective amount of a humanized or chimeric CD37-specific binding molecule derived from G28-1 and comprising a binding domain and immunoglobulin CH2 and CH3 domains, wherein the binding domain comprises a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 61;
a light chain CDR2 comprising the amino acid sequence of SEQ ID NO;
64;
a light chain CDR3 comprising the amino acid sequence of SEQ ID NO;
66;
a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO;
63;
a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO;
65; and
a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO;
67 or 68;wherein said human or chimeric CD37-specific binding molecule specifically binds human CD37 on the surface of a B-cell tumor cell in the subject.
- 61;
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6. A method of inhibiting B cell tumor growth in a subject in need thereof, the method comprising administering an effective amount of a humanized or chimeric CD37-specific binding molecule derived from G28-1 and comprising a binding domain and immunoglobulin CH2 and CH3 domains, wherein the binding domain comprises a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 61;
a light chain CDR2 comprising the amino acid sequence of SEQ ID NO;
64;
a light chain CDR3 comprising the amino acid sequence of SEQ ID NO;
66;
a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO;
63;
a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO;
65; and
a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO;
67 or 68;wherein said humanized or chimeric CD37-specific binding molecule specifically binds human CD37 on the surface of a B-cell tumor cell in the subject.
- 61;
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7. A method of inducing tyrosine phosporylation in B cell cancer cells, the method comprising contacting the B cell cancer cells with a humanized or chimeric CD37-specific binding molecule derived from G28-1 and comprising a binding domain and immunoglobulin CH2 and CH3 domains, wherein the binding domain comprises a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 61;
a light chain CDR2 comprising the amino acid sequence of SEQ ID NO;
64;
a light chain CDR3 comprising the amino acid sequence of SEQ ID NO;
66;
a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO;
63;
a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO;
65; and
a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO;
67 or 68;wherein said humanized or chimeric CD37-specific binding molecule specifically binds human CD37 on the surface of a B-cell cancer cell.
- 61;
Specification