# US 2019/0315874 A1 · IL3Ralpha Antibody Conjugates and Uses Thereof

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- Number: US 2019/0315874 A1
- Document ID: US20190315874A1
- Status: Published application
- Kind: A1
- Application number: 16/393,863
- Filed: 2019-04-24
- Published: 2019-10-17
- Earliest claimed: 2007-04-13
- Assignees: Stemline Therapeutics, Inc.
- Applicants: Stemline Therapeutics, Inc.
- Inventors: Ivan Bergstein
- Web page: https://patentgrep.com/patent/US20190315874A1

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C12N 9/1048: {Glycosyltransferases (2.4)}
- C12N 9/1077: {Pentosyltransferases (2.4.2)}
- C12N 15/86: Viral vectors
- C12Y 204/02036: NAD(+)--diphthamide ADP-ribosyltransferase (2.4.2.36)
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- C07K 16/18: against material from animals or humans
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- 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
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- C07K 2319/55: containing a fusion with a toxin, e.g. diphteria toxin
- C12N 5/163: {one of the fusion partners being a B or a T lymphocyte}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES
- 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)

## Abstract

The present invention provides antibodies that bind to the IL-3 receptor alpha subunit alpha (Il3Rα) chain, and compositions comprising such antibodies. The present invention provides methods for inhibiting or reducing an IL3Rα-expressing cell population, the methods comprising contacting a population of IL3Rα-expressing cells (e.g., cancer cells and/or cancer stem cells) with an antibody that binds to IL3Rα. The present invention also provides antibody conjugates comprising an antibody that binds to an IL3Rα chain linked to a cytotoxic agent or anticellular agent and compositions comprising such conjugates. The present invention also provides methods for preventing, treating and/or managing a disorder associated with IL3Rα-expressing cells (e.g., a hematological cancer), the methods comprising administering to a subject in need thereof an antibody that binds to IL3Rα.

## Claims

### Claim at position 1

-83. (canceled)

### Claim 84

A nucleic acid that encodes a single chain fragment variable (scFv) region of an antibody that binds CD123, wherein said nucleic acid comprises nucleotide sequences that encode the complementarity determining regions (CDRs) of the variable heavy (VH) domain and the variable light (VL) domain of said antibody, and wherein said CDRs comprise the VH domain CDR1 presented in SEQ ID NO: 13, the VH domain CDR2 presented in SEQ ID NO: 14, the VH domain CDR3 presented in SEQ ID NO: 15, the VL domain CDR1 presented in SEQ ID NO: 18, the VL domain CDR2 presented in SEQ ID NO: 19, and the VL domain CDR3 presented in SEQ ID NO: 20.

### Claim 85 (depends on 84)

The nucleic acid of claim 84, wherein said nucleotide sequence that encodes the CDRs of the VH domain of said antibody comprises SEQ ID NO: 11.

### Claim 86 (depends on 84)

The nucleic acid of claim 84, wherein said nucleotide sequence that encodes the CDRs of the VL domain of said antibody comprises SEQ ID NO: 16.

### Claim 87 (depends on 84)

The nucleic acid of claim 84, wherein said nucleotide sequence that encodes the CDRs of the VH domain of said antibody comprises SEQ ID NO: 11 and wherein said nucleotide sequence that encodes the CDRs of the VL domain of said antibody comprises SEQ ID NO: 16.

### Claim 88 (depends on 84)

The nucleic acid of claim 84, wherein said nucleic acid encodes a fusion protein, said fusion protein comprising said anti-CD123 scFv antibody region and a second protein.

### Claim 89 (depends on 88)

An expression vector comprising the nucleic acid of claim 88.

### Claim 90 (depends on 89)

The expression vector of claim 89, wherein said expression vector is a viral vector.

### Claim 91 (depends on 89)

An isolated mammalian cell comprising the expression vector of claim 89.

### Claim 92 (depends on 88)

An isolated mammalian cell engineered to express the nucleic acid of claim 88.

### Claim 93 (depends on 92)

The mammalian cell of claim 92, wherein said mammalian cell is a human cell.

### Claim 94 (depends on 88)

The nucleic acid of claim 88, wherein said second protein is Pseudomonas exotoxin A.

### Claim 95 (depends on 88)

The nucleic acid of claim 88, wherein said second protein is abrin, ricin A, cholera toxin, diphtheria toxin, tumor necrosis factor, α-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator, an apoptotic agent, a thrombotic agent, an anti-angiogenic agent, angiostatin, endostatin, a lymphokine, interleukin-1, interleukin-2, interleukin-6, granulocyte macrophage colony stimulating factor, and granulocyte colony stimulating factor, or a growth factor.

### Claim 96 (depends on 84)

An expression vector comprising the nucleic acid of claim 84.

### Claim 97 (depends on 96)

The expression vector of claim 96, wherein said expression vector is a viral vector.

### Claim 98 (depends on 96)

An isolated mammalian cell comprising the expression vector of claim 96.

### Claim 99 (depends on 84)

An isolated mammalian cell engineered to express the nucleic acid of claim 84.

### Claim 100 (depends on 99)

The mammalian cell of claim 99, wherein said mammalian cell is a human cell.

### Claim 101

A nucleic acid that encodes an anti-CD123 single chain fragment variable (scFv) antibody region, wherein said nucleic acid comprises SEQ ID NO: 11 and SEQ ID NO: 16.

### Claim 102 (depends on 101)

The nucleic acid of claim 101, wherein said nucleic acid encodes a fusion protein, said fusion protein comprising said anti-CD123 scFv antibody region and a second protein.

### Claim 103 (depends on 102)

An expression vector comprising the nucleic acid of claim 102.

### Claim 104 (depends on 103)

The expression vector of claim 103, wherein said expression vector is a viral vector.

### Claim 105 (depends on 103)

An isolated mammalian cell comprising the expression vector of claim 103.

### Claim 106 (depends on 102)

An isolated mammalian cell engineered to express the nucleic acid of claim 102.

### Claim 107 (depends on 106)

The mammalian cell of claim 106, wherein said mammalian cell is a human cell.

### Claim 108 (depends on 102)

The nucleic acid of claim 102, wherein said second protein is Pseudomonas exotoxin A.

### Claim 109 (depends on 102)

The nucleic acid of claim 102, wherein said second protein is abrin, ricin A, cholera toxin, diphtheria toxin, tumor necrosis factor, α-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator, an apoptotic agent, a thrombotic agent, an anti-angiogenic agent, angiostatin, endostatin, a lymphokine, interleukin-1, interleukin-2, interleukin-6, granulocyte macrophage colony stimulating factor, and granulocyte colony stimulating factor, or a growth factor.

### Claim 110 (depends on 101)

An expression vector comprising the nucleic acid of claim 101.

### Claim 111 (depends on 110)

The expression vector of claim 110, wherein said expression vector is a viral vector.

### Claim 112 (depends on 110)

An isolated mammalian cell comprising the expression vector of claim 110.

### Claim 113 (depends on 101)

An isolated mammalian cell engineered to express the nucleic acid of claim 101.

### Claim 114 (depends on 113)

The mammalian cell of claim 113, wherein said mammalian cell is a human cell.

### Claim 115

A nucleic acid that encodes the variable heavy (VH) domain of monoclonal antibody 32703, wherein said VH domain comprises SEQ ID NO: 12.

### Claim 116 (depends on 115)

The nucleic acid of claim 115, wherein said nucleic acid comprises SEQ ID NO: 11.

### Claim 117 (depends on 116)

The nucleic acid of claim 116, wherein said nucleic acid further comprises a nucleic acid sequence that encodes the variable light (VL) domain of monoclonal antibody 32703, wherein said VL domain comprises SEQ ID NO: 17.

### Claim 118 (depends on 117)

The nucleic acid of claim 117, wherein said nucleic acid sequence that encodes the VL domain of monoclonal antibody 32703 comprises SEQ ID NO: 16.

### Claim 119

A nucleic acid that encodes the variable light (VL) domain of monoclonal antibody 32703, wherein said VL domain comprises SEQ ID NO: 17.

### Claim 120 (depends on 119)

The nucleic acid of claim 119, wherein said nucleic acid comprises SEQ ID NO: 16.