Optimized antibodies that target HM1.24

• US 8,394,374 B2
• Filed: 09/18/2007
• Issued: 03/12/2013
• Est. Priority Date: 09/18/2006
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Bernett, Matthew J., Desjarlais, John R., Karki, Sher Bahadur, Lazar, Gregory Alan, Muchhal, Umesh S., Nguyen, Duc-Hanh Thi, Richards, John O.
• Primary Examiner(s): Goddard, Laura B
• Assistant Examiner(s): Natarajan, Meera
• Application Number:
  US12/441,885
• Publication Number:
  US 20100104557A1
• Time in Patent Office: 2,002 Days
• Field of Search: None
• US Class Current: 424/130.1
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• 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: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• 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 2317/72 Increased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present disclosure describes antibodies that target HM1.24. In various aspects, the antibodies have specific CDR, variable, or full length sequences, have modifications with the parent antibody, or include at least one one modification relative to a parent antibody that alters affinity to an FcγR or alters effector function as compared to the parent antibody. Nucleic acids encoding the antibodies and methods of using the antibodies are also disclosed.

Claims

1. A purified antibody that binds HM1.24, said antibody comprising a heavy chain and a light chain, said light chain having a CDR1 comprising the amino acid sequence of SEQ ID NO:

11, a CDR2 comprising the amino acid sequence of SEQ ID NO;

12 and a CDR3 comprising the amino acid sequence of SEQ ID NO;

13; and

said heavy chain having a CDR1 comprising the amino acid sequence of SEQ ID NOs;

14, a CDR2 comprising an amino acid sequence of SEQ ID NO;

119, and a CDR3 comprising the amino acid sequence of SEQ ID NO;

16.

2. The antibody of claim 1, wherein said heavy chain sequence further comprises a variable sequence of SEQ ID NO:

26, and said light chain sequence further comprises a variable sequence of SEQ ID NO;

20.

4. An antibody according to claim 2, wherein said antibody comprises a heavy chain sequence of SEQ ID NO:

108, and a variable light chain sequence of SEQ ID NO;

118.

3. A purified antibody that binds HM1.24, wherein said antibody comprises a heavy chain variable sequence selected from the group consisting of SEQ ID NOS:

21-32, and a light chain variable sequence selected from the group consisting of SEQ ID NOS;

17-20.

5. An antibody according to claim 3, wherein said antibody enhances ADCC effector function as compared to the parent antibody.

6. An antibody according to claim 3 further comprising an amino acid modification of 332E.

7. An antibody according to claim 6, further comprising a second amino acid modification selected from the group consisting of:

236A, 239D, 332E, 268D, 268E, 330Y, and 330L.

8. An antibody according to claim 7, wherein the second amino acid modification is 239D.

9. An antibody according to claim 3, further comprising a glycoform modification that reduces the level of fucose relative to the parent antibody.

10. A composition comprising a plurality of glycosylated antibodies as in claim 9, wherein about 80-100% of the glycosylated antibody in the composition comprises a mature core carbohydrate structure which lacks fucose.

11. A pharmaceutical composition comprising an antibody according to claim 3 and a pharmaceutically acceptable carrier.