# US 2014/0155584 A1 · Conjugated anti-cd38 antibodies

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- Number: US 2014/0155584 A1
- Document ID: US20140155584A1
- Status: Published application
- Kind: A1
- Application number: 13/977,207
- Filed: 2011-12-30
- Published: 2014-06-05
- Earliest claimed: 2010-12-30
- Assignees: Takeda Pharmaceutical Company Limited
- Inventors: Kathleen Ann Elias; Gregory Landes; Shweta Singh; Wouter Korver; Andrew Walling Drake; Mary Haak-Frendscho; Gyorgy Pal Snell; Vinay Bhaskar
- Web page: https://patentgrep.com/patent/US20140155584A1

## CPC

- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- C07K 16/40: against enzymes
- A61K 47/6871: {the antibody targeting an enzyme}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- C12N 9/99: Enzyme inactivation by chemical treatment
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- 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 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Isolated antibodies that bind to human CD38 and cynomolgus CD38 are disclosed. Also disclosed are pharmaceutical compositions comprising the disclosed antibodies, and therapeutic and diagnostic methods for using the disclosed antibodies.

## Claims

### Claim 1

An isolated antibody which specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2) comprising:
a) a heavy chain variable region comprising:
i) a first CDR comprising SEQ ID NO:3;
ii) a second CDR comprising SEQ ID NO:4;
iii) a third CDR comprising SEQ ID NO:5; and
b) a light chain variable region comprising:
i) a first CDR comprising SEQ ID NO:6;
ii) a second CDR comprising SEQ ID NO:7;
iii) a third CDR comprising SEQ ID NO:8; and
c) a covalently attached drug moiety.

### Claim 2 (depends on 1)

An isolated antibody according to claim 1 wherein said heavy chain variable region comprises SEQ ID NO:9.

### Claim 3 (depends on 1)

An isolated antibody according to claim 1 wherein said light chain variable region comprises SEQ ID NO:10.

### Claim 4 (depends on 1)

An isolated antibody according to claim 1 wherein said heavy chain variable region comprises SEQ ID NO:9 and said light chain variable region comprises SEQ ID NO:10.

### Claim 5 (depends on 1)

An isolated antibody according to claim 1 wherein the heavy chain comprises SEQ ID NO:21 and the light chain comprises SEQ ID NO:22.

### Claim 6

An isolated antibody which specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2) comprising:
a) a heavy chain variable region comprising:
i) a first CDR comprising SEQ ID NO:13;
ii) a second CDR comprising SEQ ID NO:14;
iii) a third CDR comprising SEQ ID NO:15; and
b) a light chain variable region comprising:
i) a first CDR comprising SEQ ID NO:16;
ii) a second CDR comprising SEQ ID NO:17;
iii) a third CDR comprising SEQ ID NO:18; and
c) a covalently attached drug moiety.

### Claim 7 (depends on 1)

An isolated antibody according to claim 1 wherein said heavy chain variable region comprises SEQ ID NO:19.

### Claim 8 (depends on 1)

An isolated antibody according to claim 1 wherein said light chain variable region comprises SEQ ID NO:20.

### Claim 9 (depends on 1)

An isolated antibody according to claim 1 wherein said heavy chain variable region comprises SEQ ID NO:19 and said light chain variable region comprises SEQ ID NO:20.

### Claim 10 (depends on 1)

An isolated antibody according to claim 1 wherein the heavy chain comprises SEQ ID NO:34 and the light chain comprises SEQ ID NO:35.

### Claim 11 (depends on 1, 6)

An isolated antibody according to claim 1 or 6 further comprising an Fc domain.

### Claim 12 (depends on 11)

An isolated antibody according to claim 11 wherein said Fc domain is human.

### Claim 13 (depends on 11)

An isolated antibody according to claim 11 wherein said Fc domain is a variant Fc domain.

### Claim 14

An isolated antibody according to any of the previous claims wherein said drug moiety is attached to said antibody using a linker.

### Claim 15 (depends on 14)

An isolated antibody according to claim 14 wherein said drug moiety is selected from the group consisting of an auristatin, a maytansinoid, and calicheamicin, a dolstatin, and a trichothecene.

### Claim 16 (depends on 2, 7)

An isolated nucleic acid encoding the heavy chain of claim 2 or 7.

### Claim 17

An isolated nucleic acid encoding the light chain of 3 or 8.

### Claim 18 (depends on 14, 15)

A host cell comprising the isolated nucleic acids of claim 14 or 15.

### Claim 19 (depends on 1, 6, 11)

A method of producing the antibody of claim 1 or 6 comprising culturing the host cell of claim 11 under conditions wherein said antibody is produced.

### Claim 20

A method of inhibiting the biological activity of human CD38 protein (SEQ ID NO: 1) and cynomolgus CD38 (SEQ ID NO:2) by contacting said protein with an antibody that interacts with at least K121, F135, Q139, D141, E239, W241, C275, K276, F284, P291 and E292 of SEQ ID NO:1 and SEQ ID NO:2.

### Claim 21

A method of treating cancer comprising administering to a patient in need thereof an isolated antibody which specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2) comprising:
a) a heavy chain variable region comprising:
i) a first CDR comprising SEQ ID NO:3;
ii) a second CDR comprising SEQ ID NO:4;
iii) a third CDR comprising SEQ ID NO:5; and
b) a light chain variable region comprising:
i) a first CDR comprising SEQ ID NO:6;
ii) a second CDR comprising SEQ ID NO:7;
iii) a third CDR comprising SEQ ID NO:8; and
c) a covalently attached drug moiety.