# US 2016/0257751 A1 · Antibody therapeutics that bind cd47

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- Number: US 2016/0257751 A1
- Document ID: US20160257751A1
- Status: Published application
- Kind: A1
- Application number: 15/061,771
- Filed: 2016-03-04
- Published: 2016-09-08
- Earliest claimed: 2015-03-04
- Assignees: Sorrento Therapeutics, Inc.
- Applicants: Sorrento Therapeutics, Inc.
- Inventors: Barbara A. Swanson; John Dixon Gray; Heyue Zhou
- Web page: https://patentgrep.com/patent/US20160257751A1

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/30: from tumour cells
- C07K 2317/21: from primates, e.g. man
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/90: characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

There is disclosed compositions and methods relating to or derived from anti-CD47 antibodies. More specifically, there is disclosed fully human antibodies that bind CD47, CD47-antibody binding fragments and derivatives of such antibodies, and CD47-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease.

## Claims

### Claim 1

An isolated fully human anti-CD47 antibody of an IgG class that binds to a CD47 epitope, said antibody comprising
a heavy chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO. 7, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 22, SEQ ID NO: 24, and SEQ ID NO: 32; and
a light chain variable domain sequence that is at least 95% identical to the amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 15, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30.

### Claim 2 (depends on 1)

The fully human antibody of claim 1, wherein the antibody comprises a heavy chain/light chain variable domain sequence selected from the group consisting of: SEQ ID NO. 1/SEQ ID NO. 2 (C47A8), SEQ ID NO. 1/SEQ ID NO. 4 (C47B10), SEQ ID NO:1/SEQ ID NO:8 (C47B10-1), SEQ ID NO. 1/SEQ ID NO. 5 (C47B10-1H4S), SEQ ID NO. 1/SEQ ID NO. 6 (C47B10-1F6S), SEQ ID NO. 7/SEQ ID NO. 8 (C47B10-2A9S), SEQ ID NO. 9/SEQ ID NO. 8 (C47B10-2B11S), SEQ ID NO. 10/SEQ ID NO. 4 (C47B10-2B8S), SEQ ID NO. 11/SEQ ID NO. 4 (C47B10-2C1S), SEQ ID NO. 12/SEQ ID NO. 4 (C47B10-2B9S), SEQ ID NO. 13/SEQ ID NO. 4 (2C4S), SEQ ID NO. 14/SEQ ID NO. 15 (C47B10-B1C), SEQ ID NO. 16/SEQ ID NO. 15 (C47B10-C6C), SEQ ID NO. 17/SEQ ID NO. 15 (C47B10-D3C), SEQ ID NO. 18/SEQ ID NO. 15 (C47B10-C11C), SEQ ID NO. 19/SEQ ID NO. 15 (C47B10-C11C), SEQ ID NO. 1/SEQ ID NO. 20 (C47KD8), SEQ ID NO. 1/SEQ ID NO. 21 (C47KD9), SEQ ID NO:1/SEQ ID NO:8 (C47B10-1H4S2), SEQ ID NO. 32/SEQ ID NO. 15 (C47B10-C3C), SEQ ID NO. 1/SEQ ID NO. 19 (C47K11), SEQ ID NO:22/SEQ ID NO:8 (C47B10-H3-D4), SEQ ID NO:1/SEQ ID NO:23 (C47B10-L1A-A10), SEQ ID NO:24/SEQ ID NO:8 (C47B10-H3-D3), SEQ ID NO:1/SEQ ID NO:25 (C47B10-L1A-A4), SEQ ID NO:1/SEQ ID NO:26 (C47B10-L3-B2), SEQ ID NO:1/SEQ ID NO:27 (C47A8-CA), SEQ ID NO:1/SEQ ID NO:28 (C47A8-CL), SEQ ID NO:1/SEQ ID NO:29 (C47-A8-CQ), and SEQ ID NO:1/SEQ ID NO:30 (C47A8-CS).

### Claim 3 (depends on 1)

The fully human antibody of claim 1, wherein the antibody has a KD of at least 1×10−6M.

### Claim 4

An anti-CD47 fully human antibody fragment, comprising
a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence selected from the group consisting of: SEQ ID NO: 1, SEQ ID NO. 7, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 22, SEQ ID NO: 24, and SEQ ID NO: 32; and
light chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence selected from the group consisting of: SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 15, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30,
wherein the fragment is a single chain antibody comprising a peptide linker connecting the heavy and light chain variable domains, or a Fab fragment.

### Claim 5 (depends on 4)

The fully human antibody fragment of claim 4, wherein the antibody comprises a heavy chain/light chain variable domain sequence selected from the group consisting of: SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 1/SEQ ID NO. 4, SEQ ID NO. 1/SEQ ID NO. 5, SEQ ID NO:1/SEQ ID NO:8, SEQ ID NO. 1/SEQ ID NO. 6, SEQ ID NO. 7/SEQ ID NO. 8, SEQ ID NO. 9/SEQ ID NO. 8, SEQ ID NO. 10/SEQ ID NO. 4, SEQ ID NO. 11/SEQ ID NO. 4, SEQ ID NO. 12/SEQ ID NO. 4, SEQ ID NO. 13/SEQ ID NO. 4, SEQ ID NO. 14/SEQ ID NO. 15, SEQ ID NO. 16/SEQ ID NO. 15, SEQ ID NO. 17/SEQ ID NO. 15, SEQ ID NO. 18/SEQ ID NO. 15, SEQ ID NO. 1/SEQ ID NO. 20, SEQ ID NO. 1/SEQ ID NO. 21, SEQ ID NO. 1/SEQ ID NO. 22, SEQ ID NO:1/SEQ ID NO:8, SEQ ID NO. 32/SEQ ID NO. 15, SEQ ID NO. 1/SEQ ID NO. 19, SEQ ID NO:22/SEQ ID NO:8, SEQ ID NO:1/SEQ ID NO:23, SEQ ID NO:24/SEQ ID NO:8, SEQ ID NO:1/SEQ ID NO:25, SEQ ID NO:1/SEQ ID NO:26, SEQ ID NO:1/SEQ ID NO:27, SEQ ID NO:1/SEQ ID NO:28, SEQ ID NO:1/SEQ ID NO:29, and SEQ ID NO:1/SEQ ID NO:30.

### Claim 6 (depends on 4)

The fully human antibody Fab fragment of claim 4, wherein the antibody has a KD of at least 1×10−6M.

### Claim 7 (depends on 1)

A method of treating cancer or a fibrotic disease in a subject in need thereof, the method comprising administering an effective amount of the antibody of claim 1, such that the cancer is treated.

### Claim 8 (depends on 7)

The method of claim 7, wherein the cancer is selected from the group consisting of: ovarian cancer, colon cancer, breast cancer, lung cancer, myelomas, neuroblastic-derived CNS tumors, monocytic leukemias, B-cell derived leukemias, T-cell derived leukemias, B-cell derived lymphomas, T-cell derived lymphomas, and mast cell derived tumors.

### Claim 9 (depends on 7)

The method of claim 7, wherein the fibrotic disease is selected from the group consisting of myocardial infarction, angina, osteoarthritis, pulmonary fibrosis, asthma, cystic fibrosis, bronchitis, and asthma.

### Claim 10 (depends on 7)

The method of claim 7, wherein the antibody comprises a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 1/SEQ ID NO. 4, SEQ ID NO. 1/SEQ ID NO. 5, SEQ ID NO:1/SEQ ID NO:8, SEQ ID NO. 1/SEQ ID NO. 6, SEQ ID NO. 7/SEQ ID NO. 8, SEQ ID NO. 9/SEQ ID NO. 8, SEQ ID NO. 10/SEQ ID NO. 4, SEQ ID NO. 11/SEQ ID NO. 4, SEQ ID NO. 12/SEQ ID NO. 4, SEQ ID NO. 13/SEQ ID NO. 4, SEQ ID NO. 14/SEQ ID NO. 15, SEQ ID NO. 16/SEQ ID NO. 15, SEQ ID NO. 17/SEQ ID NO. 15, SEQ ID NO. 18/SEQ ID NO. 15, SEQ ID NO. 19/SEQ ID NO. 15, SEQ ID NO. 1/SEQ ID NO. 20, SEQ ID NO. 1/SEQ ID NO. 21, SEQ ID NO. 1/SEQ ID NO. 22, SEQ ID NO:1/SEQ ID NO:8, SEQ ID NO. 32/SEQ ID NO. 15, SEQ ID NO. 1/SEQ ID NO. 19, SEQ ID NO:22/SEQ ID NO:8, SEQ ID NO:1/SEQ ID NO:23, SEQ ID NO:24/SEQ ID NO:8, SEQ ID NO:1/SEQ ID NO:25, SEQ ID NO:1/SEQ ID NO:26, SEQ ID NO:1/SEQ ID NO:27, SEQ ID NO:1/SEQ ID NO:28, SEQ ID NO:1/SEQ ID NO:29, and SEQ ID NO:1/SEQ ID NO:30.

### Claim 11 (depends on 4)

A method of treating cancer or a fibrotic disease in a subject in need thereof, the method comprising administering an effective amount of the antibody fragment of claim 4.

### Claim 12 (depends on 11)

The method of claim 11, wherein the cancer is selected from the group consisting of: ovarian cancer, colon cancer, breast cancer, lung cancer, myelomas, neuroblastic-derived CNS tumors, monocytic leukemias, B-cell derived leukemias, T-cell derived leukemias, B-cell derived lymphomas, T-cell derived lymphomas, and mast cell derived tumors.

### Claim 13 (depends on 11)

The method of claim 11, wherein the fibrotic disease is selected from the group consisting of myocardial infarction, angina, osteoarthritis, pulmonary fibrosis, asthma, cystic fibrosis, bronchitis, and asthma.

### Claim 14 (depends on 11)

The method of claim 11, wherein the antibody fragment comprises a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 1/SEQ ID NO. 4, SEQ ID NO. 1/SEQ ID NO. 5, SEQ ID NO:1/SEQ ID NO. 8, SEQ ID NO. 1/SEQ ID NO. 6, SEQ ID NO. 7/SEQ ID NO. 8, SEQ ID NO. 9/SEQ ID NO. 8, SEQ ID NO. 10/SEQ ID NO. 4, SEQ ID NO. 11/SEQ ID NO. 4, SEQ ID NO. 12/SEQ ID NO. 4, SEQ ID NO. 13/SEQ ID NO. 4, SEQ ID NO. 14/SEQ ID NO. 15, SEQ ID NO. 16/SEQ ID NO. 15, SEQ ID NO. 17/SEQ ID NO. 15, SEQ ID NO. 18/SEQ ID NO. 15, SEQ ID NO. 19/SEQ ID NO. 15, SEQ ID NO. 1/SEQ ID NO. 20, SEQ ID NO. 1/SEQ ID NO. 21, SEQ ID NO. 1/SEQ ID NO. 22, SEQ ID NO:1/SEQ ID NO. 8, SEQ ID NO. 32/SEQ ID NO. 15, SEQ ID NO. 1/SEQ ID NO. 19, SEQ ID NO. 22/SEQ ID NO. 8, SEQ ID NO:1/SEQ ID NO. 23, SEQ ID NO. 24/SEQ ID NO. 8, SEQ ID NO:1/SEQ ID NO. 25, SEQ ID NO:1/SEQ ID NO. 26, SEQ ID NO:1/SEQ ID NO. 27, SEQ ID NO:1/SEQ ID NO. 28, SEQ ID NO:1/SEQ ID NO. 29, and SEQ ID NO:1/SEQ ID NO. 30.

### Claim 15

An isolated anti-CD47 antibody, or an antigen-binding fragment thereof,
comprising a heavy chain variable domain comprising complementarity determining regions (CDRs) as set forth in a heavy chain variable domain amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO. 7, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 22, SEQ ID NO: 24, and SEQ ID NO: 32; and
comprising a light chain variable domain comprising CDRs as set forth in a light chain variable region amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 15, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30.

### Claim 16 (depends on 15)

The antibody of claim 15, wherein the antibody has CDRs from a heavy/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2 (C47A8), SEQ ID NO. 1/SEQ ID NO. 4 (C47B10), SEQ ID NO:1/SEQ ID NO:8 (C47B10-1), SEQ ID NO. 1/SEQ ID NO. 5 (C47B10-1H4S), SEQ ID NO. 1/SEQ ID NO. 6 (C47B10-1F6S), SEQ ID NO. 7/SEQ ID NO. 8 (C47B10-2A9S), SEQ ID NO. 9/SEQ ID NO. 8 (C47B10-2B11S), SEQ ID NO. 10/SEQ ID NO. 4 (C47B10-2B8S), SEQ ID NO. 11/SEQ ID NO. 4 (C47B10-2C1S), SEQ ID NO. 12/SEQ ID NO. 4 (C47B10-2B9S), SEQ ID NO. 13/SEQ ID NO. 4 (2C4S), SEQ ID NO. 14/SEQ ID NO. 15 (C47B10-B1C), SEQ ID NO. 16/SEQ ID NO. 15 (C47B10-C6C), SEQ ID NO. 17/SEQ ID NO. 15 (C47B10-D3C), SEQ ID NO. 18/SEQ ID NO. 15 (C47B10-C11C), SEQ ID NO. 19/SEQ ID NO. 15 (C47B10-C11C), SEQ ID NO. 1/SEQ ID NO. 20 (C47KD8), SEQ ID NO. 1/SEQ ID NO. 21 (C47KD9), SEQ ID NO:1/SEQ ID NO:8 (C47B10-1H4S2), SEQ ID NO. 32/SEQ ID NO. 15 (C47B10-C3C), SEQ ID NO. 1/SEQ ID NO. 19 (C47K11), SEQ ID NO:22/SEQ ID NO:8 (C47B10-H3-D4), SEQ ID NO:1/SEQ ID NO:23 (C47B10-L1A-A10), SEQ ID NO:24/SEQ ID NO:8 (C47B10-H3-D3), SEQ ID NO:1/SEQ ID NO:25 (C47B10-L1A-A4), SEQ ID NO:1/SEQ ID NO:26 (C47B10-L3-B2), SEQ ID NO:1/SEQ ID NO:27 (C47A8-CA), SEQ ID NO:1/SEQ ID NO:28 (C47A8-CL), SEQ ID NO:1/SEQ ID NO:29 (C47-A8-CQ), and SEQ ID NO:1/SEQ ID NO:30 (C47A8-CS).

### Claim 17 (depends on 15)

The antibody, or antigen-binding fragment thereof, of claim 15, which has a KD of at least 1×10−6M.

### Claim 18 (depends on 15)

A pharmaceutical composition comprising the anti-CD47 antibody, or antibody fragment of claim 15, and a pharmaceutically acceptable carrier.

### Claim 19 (depends on 15)

A method of treating cancer or a fibrotic disease in a human subject in need thereof, comprising administering an effective amount of the anti-CD47 antibody, or antigen-binding fragment thereof, of claim 15 to the subject, such that cancer or the fibrotic disease is treated.

### Claim 20 (depends on 19)

The method of claim 19, wherein the cancer is selected from the group consisting of: ovarian cancer, colon cancer, breast cancer, lung cancer, myelomas, neuroblastic-derived CNS tumors, monocytic leukemias, B-cell derived leukemias, T-cell derived leukemias, B-cell derived lymphomas, T-cell derived lymphomas, and mast cell derived tumors or the fibrotic disease is selected from the group consisting of: myocardial infarction, angina, osteoarthritis, pulmonary fibrosis, asthma, cystic fibrosis, bronchitis, and asthma.