# US 9,040,042 B2 · Optimized antibodies that target HM1.24

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- Number: US 9,040,042 B2
- Document ID: US9040042B2
- Status: Granted
- Kind: B2
- Application number: 13/794,676
- Filed: 2013-03-11
- Published: 2014-07-24
- Granted: 2015-05-26
- Earliest claimed: 2006-09-18
- Assignees: Xencor, Inc.
- Applicants: Matthew J. Bernett; John R. Desjarlais; Sher Bahadur Karki; Gregory Alan Lazar; Umesh S. Muchhal; Duc-Hanh Thi Nguyen; John O. Richards
- Inventors: Matthew J. Bernett; John R. Desjarlais; Sher Bahadur Karki; Gregory Alan Lazar; Umesh S. Muchhal; Duc-Hanh Thi Nguyen; John O. Richards
- Web page: https://patentgrep.com/patent/US9040042B2

## CPC

- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 31/69: Boron compounds
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/72: Increased effector function due to an Fc-modification
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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 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

### Claim 1

A method of treating a subject having a plasma cell related disease, wherein said method comprises administering to said subject an 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.

### Claim 2 (depends on 1)

A method of claim 1, wherein said disease is selected from the group consisting of multiple myeloma(MM), mantle cell myeloma (MCM), myelodysplastic syndrome with del5q (MDS), and autoimmune indication.

### Claim 3 (depends on 1)

A method of claim 1, wherein said disease is an autoimmune disease.

### Claim 4 (depends on 3)

The method of claim 3, wherein said autoimmune disease is selected from the group consisting of: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE or lupus), multiple sclerosis, Sjogren's syndrome, and idiopathic thrombocytopenia purpura (ITP).

### Claim 5 (depends on 1)

The method of claim 1 further comprising administering a compound selected from the group consisting of bortezomib, lenalidomide, and dexamethasone.

### Claim 6 (depends on 1)

The method 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.

### Claim 7 (depends on 6)

The method of claim 6, wherein said antibody comprises a heavy chain sequence of SEQ ID NO:108, and a variable light chain sequence of SEQ ID NO:118.

### Claim 8

A method of treating a subject having a plasma cell related disease, wherein said method comprises administering to said subject an antibody that binds HM1.24, said antibody comprising,
a heavy chain and a light chain,
wherein said heavy chain comprises a heavy chain variable sequence selected from the group consisting of SEQ ID NOS: 21-32, and
wherein said light chain comprises a light chain variable sequence selected from the group consisting of SEQ ID NOS:17-20.

### Claim 9 (depends on 8)

The method of claim 8, wherein said antibody enhances ADCC effector function as compared to the parent antibody.

### Claim 10 (depends on 8)

The method of claim 8, further comprising an amino acid modification of 332E.

### Claim 11 (depends on 10)

The method of claim 10, further comprising a second amino acid modification selected from the group consisting of: 236A, 239D, 332E, 268D, 268E, 330Y, and 330L.

### Claim 12 (depends on 10)

The method of claim 10, wherein the second amino acid modification is 239D.

### Claim 13 (depends on 12)

The method of claim 12, wherein said disease is selected from the group consisting of multiple myeloma(MM), mantle cell myeloma (MCM), myelodysplastic syndrome with del5q (MDS), and autoimmune indication.

### Claim 14 (depends on 12)

The method of claim 12, wherein said disease is an autoimmune disease.

### Claim 15 (depends on 14)

The method of claim 14, wherein said autoimmune disease is selected from the group consisting of: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE or lupus), multiple sclerosis, Sjogren's syndrome, and idiopathic thrombocytopenia purpura (ITP).

### Claim 16 (depends on 12)

The method of claim 12 further comprising administering a compound selected from the group consisting of bortezomib, lenalidomide, and dexamethasone.

### Claim 17 (depends on 7)

The method of claim 7, wherein said disease is selected from the group consisting of multiple myeloma(MM), mantle cell myeloma (MCM), myelodysplastic syndrome with del5q (MDS), and autoimmune indication.

### Claim 18 (depends on 7)

The method of claim 7, wherein said disease is an autoimmune disease.

### Claim 19 (depends on 18)

The method of claim 18, wherein said autoimmune disease is selected from the group consisting of: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE or lupus), multiple sclerosis, Sjogren's syndrome, and idiopathic thrombocytopenia purpura (ITP).

### Claim 20 (depends on 7)

The method of claim 7 further comprising administering a compound selected from the group consisting of bortezomib, lenalidomide, and dexamethasone.