# US 11,079,381 B2 · Risk-stratification of B-precursor acute lymphoblastic leukemia patients

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- Number: US 11,079,381 B2
- Document ID: US11079381B2
- Status: Granted
- Kind: B2
- Application number: 15/313,136
- Filed: 2015-05-20
- Published: 2017-05-04
- Granted: 2021-08-03
- Earliest claimed: 2014-05-30
- Assignees: Amgen Research (Munich) GmbH; Amgen Inc.
- Applicants: Amgen Research (Munich) GmbH; Amgen Inc.
- Inventors: Gerhard Zugmaier; Peter Kufer; Shilpa Alekar
- Web page: https://patentgrep.com/patent/US11079381B2

## CPC

- G01N 33/57505: of the blood, e.g. leukaemia
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61P 25/00: Drugs for disorders of the nervous system
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- G01N 33/5091: {for testing the pathological state of an organism}
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- C07K 2317/31: multispecific
- C07K 2317/622: Single chain antibody (scFv)
- G01N 2333/70503: Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- G01N 2800/50: Determining the risk of developing a disease
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- G01N 2800/56: Staging of a disease; Further complications associated with the disease
- 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)
- 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 invention relates to a method for risk-stratifying subjects suffering from B-precursor acute lymphoblastic leukemia (ALL), wherein said subjects are intended for a therapy comprising administration of a CD3 binding domain. Risk-stratification is based on the determination of the amount blast cells in a bone marrow sample from said subject, and/or on the determination of the number of blast cells per 1 μl in a CSF sample from said subject. According to the category into which subjects are risk-stratified, said subjects can be appropriately treated, while their risk of a potential adverse neurological reaction can be reduced or even excluded.

## Claims

### Claim 1

A method of treating B-precursor acute lymphoblastic leukemia (ALL) in a subject determined to be at a reduced risk for developing a potential adverse neurological reaction from a therapy which comprises re-directing of T-cells against target cells, comprising selecting said subject for having a reduced risk when the subject has been determined as having
at least 20% blast cells per 200 counted bone marrow cells in a bone marrow sample; and
administering to said subject determined to be at a reduced risk said therapy which comprises re-directing of T-cells against target cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the neurological reaction is one or more selected from the group consisting of: confusion, ataxia, disorientation, dysphasia, aphasia, speech impairment, cerebellar symptoms, tremor, apraxia, seizure, grand mal convulsion, palsy, and balance disorder.

### Claim 3 (depends on 1)

The method of claim 1, wherein said therapy which comprises re-directing of T-cells against target cells in a subject, includes a CD3 binding domain.

### Claim 4 (depends on 3)

The method of claim 3, wherein said CD3 binding domain is part of a bispecific single chain antibody.

### Claim 5 (depends on 4)

The method of claim 4, wherein said bispecific single chain antibody is a CD19×CD3 bispecific single chain antibody.

### Claim 6 (depends on 5)

The method of claim 5, wherein said CD19×CD3 bispecific single chain antibody is blinatumomab (AMG 103).

### Claim 7 (depends on 1)

The method of claim 1, wherein said therapy includes a genetically engineered T-cell having a chimeric antigen receptor (CAR).

### Claim 8 (depends on 1)

The method of claim 1, wherein said subject is a human.