# US 11,078,272 B2 · Treatment of pediatric brain tumors with targeting of CD47 pathway

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- Number: US 11,078,272 B2
- Document ID: US11078272B2
- Status: Granted
- Kind: B2
- Application number: 15/912,447
- Filed: 2018-03-05
- Published: 2018-09-13
- Granted: 2021-08-03
- Earliest claimed: 2017-03-09
- Assignees: The Board of Trustees of the Leland Stanford Junior University
- Applicants: The Board of Trustees of the Leland Stanford Junior University
- Inventors: Sharareh Gholamin; Samuel Cheshier; Siddhartha S. Mitra; Irving L. Weissman
- Web page: https://patentgrep.com/patent/US11078272B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 9/0004: {Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas}
- A61P 35/00: Antineoplastic agents
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Methods are provided for targeting pediatric brain tumor cells for depletion.

## Claims

### Claim 1

A method of treating a metastatic pediatric brain tumor in an individual, the method comprising:
administering by direct central nervous system delivery to the individual with a pediatric brain tumor anti-CD47 antibody hu5F9-G4 at a dose of from 10 mg/kg to 50 mg/kg effective to increase depletion of pediatric brain tumor cell and reduce metastasis to the meninges and/or spine.

### Claim 2 (depends on 1)

The method of claim 1, wherein the metastatic pediatric brain tumor is a malignant glioma.

### Claim 3 (depends on 2)

The method of claim 2, wherein the glioma is a high grade glioblastoma.

### Claim 4 (depends on 2)

The method of claim 2, wherein the glioma is diffuse intrinsic pontine glioma.

### Claim 5 (depends on 1)

The method of claim 1, wherein the pediatric brain tumor is an embryonal cancer selected from medulloblastoma, atypical teratoid rhabdoid tumor, and primitive neuroectodermal tumor.

### Claim 6 (depends on 1)

The method of claim 1, wherein the metastatic pediatric brain tumor is a medulloblastoma.

### Claim 7 (depends on 1)

The method of claim 1, wherein the metastatic pediatric brain tumor is an atypical teratoid rhabdoid tumor.

### Claim 8 (depends on 1)

The method of claim 1, wherein the metastatic pediatric brain tumor is a primitive neuroectodermal tumor.

### Claim 9

A method of treating a metastatic pediatric brain tumor in an individual, the method comprising:
administering to the individual with a pediatric brain tumor by direct central nervous system delivery with an implantable continuous delivery device implanted in the ventricles of the brain, anti-CD47 antibody hu5F9-G4 at a dose of from 10 mg/kg to 50 mg/kg effective to increase depletion of pediatric brain tumor cells and reduce metastasis to the meninges and/or spine.

### Claim 10 (depends on 9)

The method of claim 9, wherein anti-CD47 antibody hu5F9-G4 is also delivered systemically.

### Claim 11 (depends on 1)

The method of claim 1, further comprising administration of a priming dose of the hu5F9-G4 antibody.

### Claim 12

A method of treating metastasis to the meninges and/or spine for a pediatric medulloblastoma in an individual, the method comprising:
administering by intraventricular CNS administration to the individual with a metastatic pediatric medulloblastoma anti-CD47 antibody hu5F9-G4 at a dose of from 10 mg/kg to 50 mg/kg effective to increase depletion of medulloblastoma cells metastasized to the meninges and/or spine; and
administering systemically anti-CD47 antibody hu5F9-G4 at a dose of from 10 mg/kg to 50 mg/kg effective to decrease volume of the primary tumor.