# US 2014/0193425 A1 · Treatment of cancer with alk1 antagonists

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2014/0193425 A1
- Document ID: US20140193425A1
- Status: Published application
- Kind: A1
- Application number: 14/046,195
- Filed: 2013-10-04
- Published: 2014-07-10
- Earliest claimed: 2012-10-05
- Assignees: Acceleron Pharma Inc.
- Applicants: Acceleron Pharma, Inc.
- Inventors: John Knopf; Ravindra Kumar; Robert S. Pearsall; Matthew L. Sherman
- Web page: https://patentgrep.com/patent/US20140193425A1

## CPC

- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 38/1709: {from mammals}
- A61K 38/1741: {alpha-Glycoproteins}
- A61K 38/1875: {Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor}
- A61K 38/45: Transferases (2)
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/40: against enzymes
- G01N 33/6863: {Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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)
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Methods for evaluating responsiveness of a subject having cancer to treatment with an activin receptor-like kinase 1 (ALK1) antagonist are provided. Methods for selecting a subject for treatment with an ALK1 antagonist based on the subject being identified as responsive to such treatment are also provided. Some of the diagnostic methods provided herein are based on detecting an ALK1 agonist, e.g., an ALK1 ligand such as BMP9 or BMP10, in a sample obtained from the subject. Diagnostic reagents and kits for determining whether a subject is responsive to treatment with an ALK1 antagonist are also provided.

## Claims

### Claim 1

A method for evaluating responsiveness of a subject to treatment with an activin receptor-like kinase 1 (ALK1) antagonist, the method comprising:
(a) determining a level of bone morphogenetic protein 9 (BMP9) and/or bone morphogenetic protein 10 (BMP10) in a sample obtained from the subject; and
(b) comparing the level of BMP9 and/or BMP 10 determined in (a) to a reference level, wherein
(i) if the level determined in (a) is higher than the reference level, the subject is identified as responsive to treatment with the ALK1 antagonist; or
(ii) if the level determined in (a) is the same or lower than the reference level, the subject is identified as not responsive to treatment with the ALK1 antagonist.

### Claim 2 (depends on 1)

The method of claim 1, wherein the ALK1 antagonist comprises an agent selected from the group consisting of an ALK1-Fc fusion protein, an ALK1 extracellular domain (ALK-ECD), an antibody or antibody fragment specifically binding ALK1, an antibody or antibody fragment specifically binding an ALK1 ligand, an endoglin ECD antibody, an endoglin ECD, a BMP9 pro-peptide, and a BMP10 pro-peptide.

### Claim 3 (depends on 1)

The method of claim 1, wherein the ALK1 antagonist comprises a polypeptide that is at least 95% identical to the polypeptide provided in SEQ ID NO: 3.

### Claim 4 (depends on 1)

The method of claim 1, wherein the level of BMP9 and/or BMP10 is determined in a sample obtained from the subject.

### Claim 5 (depends on 4)

The method of claim 4, wherein the sample is a tissue sample or body fluid sample.

### Claim 6 (depends on 5)

The method of claim 5, wherein the tissue sample comprises a tumor tissue or a tumor cell.

### Claim 7

(canceled)

### Claim 8 (depends on 1)

The method of claim 1, wherein the level of BMP9 and/or BMP10 is determined by measuring the level of a BMP9 and/or BMP10 gene product.

### Claim at position 9

9-10. (canceled)

### Claim 11 (depends on 1)

The method of claim 1, wherein the subject is diagnosed with or is suspected to have a cancer.

### Claim at position 11

12-14. (canceled)

### Claim 15

A method of treating a subject with an ALK1 antagonist, the method comprising:
(a) selecting the subject for treatment with an ALK1 antagonist on the basis that the subject exhibits a level of BMP9 and/or BMP10 that is higher than a reference level; and
(b) administering the ALK1 antagonist to the subject.

### Claim 16 (depends on 15)

The method of claim 15, wherein the subject is diagnosed with or is suspected to have a cancer.

### Claim 17 (depends on 16)

The method of claim 16, wherein the cancer is breast cancer, multiple myeloma, cervical cancer, colorectal cancer, endometrial cancer, head and neck cancer, liver cancer, lung cancer, malignant carcinoid, malignant glioma, malignant lymphoma, malignant melanoma, ovarian cancer, or pancreatic cancer.

### Claim 18 (depends on 16)

The method of claim 16, wherein the cancer is resistant to an angiogenesis inhibitor not comprising an ALK1 antagonist.

### Claim 19 (depends on 15)

The method of claim 15, wherein the ALK1 antagonist comprises an agent selected from the group consisting of an ALK1-Fc fusion protein, an ALK1 extracellular domain (ALK-ECD), an antibody or antibody fragment specifically binding ALK1, an antibody or antibody fragment specifically binding an ALK1 ligand, an endoglin ECD antibody, an endoglin ECD, a BMP9 pro-peptide, and a BMP10 pro-peptide.

### Claim 20 (depends on 15)

The method of claim 15, wherein the ALK1 antagonist comprises a polypeptide that is at least 95% identical to the polypeptide provided in SEQ ID NO: 3.

### Claim 21

(canceled)

### Claim 22

A diagnostic kit for evaluating responsiveness of a subject to treatment with an activin receptor-like kinase 1 (ALK1) antagonist, the kit comprising:
an agent for detecting a BMP9 and/or BMP10 gene product in a sample; and
instructions for detecting and/or quantifying a BMP9 and/or BMP 10 gene product.

### Claim 23 (depends on 22)

The kit of claim 22, wherein the gene product is a protein.

### Claim 24 (depends on 22)

The kit of claim 22, wherein the gene product is a transcript.

### Claim 25 (depends on 22)

The kit of claim 22, wherein the agent is a binding agent that specifically binds the BMP9 and/or BMP 10 gene product.

### Claim 26 (depends on 25)

The kit of claim 25 wherein the binding agent is an antibody or an antibody fragment that specifically bind the gene product.

### Claim at position 24

27-29. (canceled)

### Claim 30 (depends on 22)

The kit of claim 22, wherein the kit further comprises instructions for quantifying the level of BMP9 and/or BMP10.

### Claim at position 26

31-52. (canceled)