# US 10,308,713 B2 · Anti-CS1 antibodies and antibody drug conjugates

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- Number: US 10,308,713 B2
- Document ID: US10308713B2
- Status: Granted
- Kind: B2
- Application number: 15/819,153
- Filed: 2017-11-21
- Published: 2018-08-09
- Granted: 2019-06-04
- Earliest claimed: 2014-10-31
- Assignees: AbbVie Biotherapeutics Inc.
- Applicants: AbbVie Biotherapeutics Inc.
- Inventors: Kurt C. Gish; Han K. Kim; Louie Naumovski
- Web page: https://patentgrep.com/patent/US10308713B2

## CPC

- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 47/6803: {Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates}
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/68035: {the drug being a pyrrolobenzodiazepine}
- A61K 47/68037: {the drug being a camptothecin [CPT] or derivatives}
- A61K 47/6813: {the drug being a peptidic cytokine, e.g. an interleukin or interferon}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6867: {the tumour determinant being from a cell of a blood cancer}
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 35/00: Antineoplastic agents
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2806: {against CD2}
- A61K 2039/505: {comprising antibodies}
- A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- 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 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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
- 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)

## Abstract

The present disclosure provides antibodies and antibody drug conjugates that bind human CS1 and their uses to treat subjects diagnosed with a plasma cell neoplasm, for example, multiple myeloma.

## Claims

### Claim 1

An antibody drug conjugate (“ADC”) comprising a cytotoxic and/or cytostatic agent linked to an antibody by way of a linker, wherein the antibody comprises six CDRs in which:
VH CDR#1 has an amino acid sequence DYYMA (SEQ ID NO:100),
VH CDR#2 has an amino acid sequence SINYDGSSTYYVDSVKG (SEQ ID NO:104),
VH CDR#3 has an amino acid sequence DRGYYFDY (SEQ ID NO:111),
VL CDR#1 has an amino acid sequence RSSQSLVHSNGNTYLH (SEQ ID NO:114),
VL CDR#2 has an amino acid sequence KVSNRFS (SEQ ID NO:121), and
VL CDR#3 has an amino acid sequence SQSTHVPPFT (SEQ ID NO:123).

### Claim 2 (depends on 1)

The ADC of claim 1, wherein the antibody comprises a VH chain corresponding in sequence to SEQ ID NO:8 and a VL chain corresponding in sequence to SEQ ID NO:10.

### Claim 3 (depends on 1)

The ADC of claim 1, wherein the antibody comprises a heavy chain corresponding in sequence to SEQ ID NO:34 and a light chain corresponding in sequence to SEQ ID NO:35.

### Claim 4 (depends on 1)

The ADC of claim 1, wherein the antibody is an IgG1.

### Claim 5 (depends on 1)

The ADC of claim 1 which has an average drug-to-antibody ratio in the range of 1-10.

### Claim 6 (depends on 1)

The ADC of claim 1 which has an average drug-to-antibody ratio in the range of 2-4.

### Claim 7 (depends on 1)

The ADC of claim 1 in which the cytotoxic and/or cytostatic agent is selected from the group consisting of calicheamicin, a maytanisoid, an auristatin and doxorubicin.

### Claim 8 (depends on 1)

The ADC of claim 1 in which the cytotoxic and/or cytostatic agent is an auristatin.

### Claim 9 (depends on 1)

The ADC of claim 1 in which the cytotoxic and/or cytostatic agent is monomethyl auristatin E or monomethyl auristatin F.

### Claim 10

An antibody drug conjugate (“ADC”) comprising a cytotoxic and/or cytostatic agent linked to an antibody by way of a linker, wherein the ADC has a structure according to formula (I):
[D-L-XY-]n-Ab (I)
or a salt thereof, wherein:
D is the antineoplastic drug;
L is the linker;
Ab is the antibody;
XY represents a covalent linkage linking linker L to antibody Ab; and
n is an integer ranging from 2 to 8;
and wherein Ab comprises six CDRs in which:
VH CDR#1 has an amino acid sequence DYYMA (SEQ ID NO:100),
VH CDR#2 has an amino acid sequence SINYDGSSTYYVDSVKG (SEQ ID NO:104),
VH CDR#3 has an amino acid sequence DRGYYFDY (SEQ ID NO:111),
VL CDR#1 has an amino acid sequence RSSQSLVHSNGNTYLH (SEQ ID NO:114),
VL CDR#2 has an amino acid sequence KVSNRFS (SEQ ID NO:121), and
VL CDR#3 has an amino acid sequence SQSTHVPPFT (SEQ ID NO:123).

### Claim 11 (depends on 10)

The ADC of claim 10 in which n is 2, 3 or 4.

### Claim 12 (depends on 10)

The ADC of claim 10 in which XY is a linkage formed with a sulfydryl group on antibody Ab.

### Claim 13 (depends on 10)

The ADC of claim 10 in which the compound according to structural formula (I) has the structure of formula (IIa):
where Ab is an antibody having a VH chain corresponding in sequence to SEQ ID NO:8 and a VL chain corresponding in sequence to SEQ ID NO:10.

### Claim 14 (depends on 13)

The ADC of claim 13 in which n is 2 or 4.

### Claim 15 (depends on 13)

The ADC of claim 13 in which D is an auristatin.

### Claim 16 (depends on 10)

The ADC of claim 10 which has the structure:
where Ab is an antibody having a VH chain corresponding in sequence to SEQ ID NO:8 and a VL chain corresponding in sequence to SEQ ID NO:10, and n is 2 or 4.

### Claim 17 (depends on 16)

The ADC of claim 16, wherein n is 2.

### Claim 18 (depends on 16)

The ADC of claim 16, wherein Ab is an antibody having a heavy chain corresponding in sequence to SEQ ID NO:34 and a light chain corresponding in sequence to SEQ ID NO:35.

### Claim 19 (depends on 18)

The ADC of claim 18, wherein n is 2.

### Claim 20

A composition comprising an antibody-drug conjugate (“ADC”) and a carrier, excipient or diluent,
wherein the ADC comprises a cytotoxic and/or cytostatic agent linked to an antibody by way of a linker, the antibody comprising six CDRs in which:
VH CDR#1 has an amino acid sequence DYYMA (SEQ ID NO:100),
VH CDR#2 has an amino acid sequence SINYDGSSTYYVDSVKG (SEQ ID NO:104),
VH CDR#3 has an amino acid sequence DRGYYFDY (SEQ ID NO:111),
VL CDR#1 has an amino acid sequence RSSQSLVHSNGNTYLH (SEQ ID NO:114),
VL CDR#2 has an amino acid sequence KVSNRFS (SEQ ID NO:121), and
VL CDR#3 has an amino acid sequence SQSTHVPPFT (SEQ ID NO:123).