B-cell reduction using CD37-specific and CD20-specific binding molecules

• US 10,143,748 B2
• Filed: 03/15/2013
• Issued: 12/04/2018
• Est. Priority Date: 07/25/2005
• Status: Expired due to Fees

• Current Assignee: Aptevo Reseach And Development LLC
• Original Assignee: Aptevo Reseach And Development LLC
• Inventors: Grosmaire, Laura Sue, Hayden-Ledbetter, Martha Susan, Ledbetter, Jeffrey A., Thompson, Peter Armstrong, Simon, Sandy Alexander, Brady, William
• Primary Examiner(s): Belyavskyi, Michail A
• Application Number:
  US13/836,103
• Publication Number:
  US 20140004117A1
• Time in Patent Office: 2,090 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2887 : against CD20
• CPC Class Codes: C07K 16/2896 : against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C07K 16/3061 : Blood cells
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/52 : Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/53 : Hinge
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/72 : Increased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 : Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 : Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/75 : Agonist effect on antigen
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding

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.

Claims

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.

2. The method of claim 1, wherein the disease or disorder is a B cell cancer or an autoimmune disease.

3. The method of claim 2, wherein the B cell cancer is selected from the group consisting of Hodgkin'"'"'s disease, non-Hodgkins lymphoma (NHL), central nervous system lymphomas, leukemias, myelomas, small lymphocytic lymphoma, B-cell ‘

prolymphocytic leukemia, lymphoplasmacytic lymphoma, splenic marginal zone lymphoma, plasma cell myeloma, solitary plasmacytoma of bone, extraosseous plasmacytoma, extranodal marginal zone B-cell lymphoma of mucosa-associated (MALT) lymphoid tissue, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt lymphoma/leukemia, B-cell proliferations of uncertain malignant potential, lymphomatoid granulomatosis, and post-transplant lymphoproliferative disorder.

4. The method of claim 2, wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Crohn'"'"'s disease, Sjogren'"'"'s syndrome, Grave'"'"'s disease, type I diabetes mellitus, psoriasis, immune thrombocytopenic purpura, pemphigus, idiopathic inflammatory myopathy, myasthenis gravis, and Waldenstorm'"'"'s macroglobinemia.

8. The method of claim 3, wherein the leukemia is acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hairy cell leukemia or chronic myoblastic leukemia.

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.

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.

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.