# US 2023/0408490 A1 · Systems and methods for testing and screening using compound bound substrates

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- Number: US 2023/0408490 A1
- Document ID: US20230408490A1
- Status: Published application
- Kind: A1
- Application number: 18/243,045
- Filed: 2023-09-06
- Published: 2023-12-21
- Earliest claimed: 2016-12-23
- Assignees: Cerus Corporation
- Applicants: Cerus Corporation
- Inventors: Anne NORTH; Naheed MUFTI
- Web page: https://patentgrep.com/patent/US20230408490A1

## CPC

- G01N 33/502: {for testing non-proliferative effects}
- G01N 33/555: Red blood cell
- 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

The present disclosure provides compositions, methods, kits and systems for detecting antibodies in a biological sample. In some embodiments, methods/systems are particularly useful for detecting antibodies in patients against pathogen-inactivating compound treated RBCs.

## Claims

### Claim at position 1

1-43. (canceled)

### Claim 44

A method of testing a sample for the presence of antibodies reactive to pathogen-inactivated red blood cells, the method comprising:
a) providing a sample from a potential recipient of an infusion of the pathogen-inactivated red blood cells, wherein the sample comprises serum or plasma;
b) contacting the sample with red blood cells, wherein a moiety is bound to the surface of the red blood cells; and wherein the moiety is selected from the group consisting of compounds of any of the following Formulae:
wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8 and R9 is —V—X-E,
wherein V is independently —R11—, —NH—R11— or —N(CH3)—R11—, where —R11— is independently —C1-8alkyl-, —C1-8heteroalkyl-, -aryl-, -heteroaryl-, —C1-3alkyl-aryl-, —C1-3heteroalkyl -aryl-, —C1-3alkyl-heteroaryl-, —C1-3heteroalkyl-heteroaryl-, -aryl-C1-3alkyl-, -aryl-C1-3heteroalkyl-, -heteroaryl-C1-3alkyl-, -heteroaryl-C1-3heteroalkyl-, —C1-3alkyl-aryl-C1-3 alkyl-, —C1-3heteroalkyl-aryl-C1-3 alkyl-, —C1-3alkyl-heteroaryl-C1-3 alkyl-, —C1-3alkyl-aryl-C1-3 heteroalkyl-, —C1-3heteroalkyl-heteroaryl-C1-3 alkyl-, —C1-3heteroalkyl-aryl-C1-3 heteroalkyl-, —C1-3alkyl-heteroaryl-C1-3 heteroalkyl-, or —C1-3heteroalkyl-heteroaryl-C1-3 heteroalkyl-;
X is independently —R11—; and
E is independently selected from the group consisting of —N(R12)2, —N(R12)(R13), —S—R12, and
where —R12 is —CH2CH2-G, where each G is
independently —Cl, —Br, —I, —O—S(═O)2—CH3, —O—S(═O)2—CH2—C6H5, or —O—S(═O)2—C6H4—CH3; and
where R13 is independently —C1-8 alkyl, —C1-8 heteroalkyl, -aryl, -heteroaryl, —C1-3alkyl-aryl, —C1-3heteroalkyl-aryl, —C1-3alkyl-heteroaryl, —C1-3heteroalkyl-heteroaryl, -aryl-C1-3alkyl, -aryl-C1-3heteroalkyl, -heteroaryl-C1-3alkyl, -heteroaryl-C1-3 heteroalkyl, —C1-3alkyl-aryl-C1-3 alkyl, —C1-3heteroalkyl-aryl-C1-3 alkyl, —C1-3alkyl-heteroaryl-C1-3 alkyl, —C1-3alkyl-aryl-C1-3 heteroalkyl, —C1-3heteroalkyl-heteroaryl-C1-3 alkyl, —C1-3heteroalkyl-aryl-C1-3 heteroalkyl, —C1-3alkyl-heteroaryl-C1-3 heteroalkyl, or —C1-3heteroalkyl-heteroaryl-C1-3 heteroalkyl;
and the remainder of R1, R2, R3, R4, R5, R6, R7, and R8 are independently selected from the group consisting
of —H, —R10, —O—R10, —NO2, —NH2, —NH—R10, —N(R10)2, —F, —Cl, —Br, —I, —C(═O)—R10, —C(═O)—O—R10, and —O—C(═O)—R10,
where —R10 is independently
H, —C1-8alkyl, —C1-8heteroalkyl, -aryl, -heteroaryl, —C1-3alkyl-aryl, —C1-3heteroalkyl-aryl, —C1-3alkyl -heteroaryl, —C1-3heteroalkyl-heteroaryl, -aryl-C1-3alkyl, -aryl-C1-3heteroalkyl, -heteroaryl-C1-3alkyl, -heteroaryl-C1-3heteroalkyl, —C1-3alkyl-aryl-C1-3 alkyl, —C1-3heteroalkyl-aryl-C1-3 alkyl, —C1-3alkyl-heteroaryl-C1-3 alkyl, —C1-3alkyl-aryl-C1-3 heteroalkyl, —C1-3heteroalkyl-heteroaryl-C1-3 alkyl, —C1-3heteroalkyl-aryl-C1-3 heteroalkyl, —C1-3alkyl-heteroaryl-C1-3 heteroalkyl, or —C1-3heteroalkyl-heteroaryl-C1-3 heteroalkyl;
where R1, R2, R3, R4, R5, R6, R7, and R8 are independently selected from the group consisting of —H, —R10, —O—R10, —NO2, —NH2, —NH—R10, —N(R10)2, —F, —Cl, —Br, —I, —C(═O)—R10, —C(═O)—O—R10, and —O—C(═O)—R10, where —R10 is independently H, —C1-8 alkyl, —C1-8 heteroalkyl, -aryl, -heteroaryl, —C1-3alkyl-aryl, —C1-3heteroalkyl-aryl, —C1-3alkyl-heteroaryl, —C1-3heteroalkyl-heteroaryl, -aryl-C1-3alkyl, -aryl-C1-3heteroalkyl, -heteroaryl-C1-3alkyl, -heteroaryl-C1-3 heteroalkyl, —C1-3alkyl-aryl-C1-3 alkyl, —C1-3heteroalkyl-aryl-C1-3 alkyl, —C1-3alkyl-heteroaryl-C1-3 alkyl, —C1-3alkyl-aryl-C1-3 heteroalkyl, —C1-3heteroalkyl-heteroaryl-C1-3 alkyl, —C1-3heteroalkyl-aryl-C1-3 heteroalkyl, —C1-3alkyl-heteroaryl-C1-3 heteroalkyl, or —C1-3heteroalkyl-heteroaryl-C1-3 heteroalkyl;
R20 is —H or —CH3; and
R21 is —R11—X-E, where —R11— is independently —C1-8alkyl-, -C18heteroalkyl-, -aryl-, -heteroaryl-, —C1-3alkyl-aryl-, —C1-3heteroalkyl -aryl-, —C1-3alkyl-heteroaryl-, —C1-3heteroalkyl-heteroaryl-, -aryl-C1-3alkyl-, -aryl-C1-3heteroalkyl-, -heteroaryl-C1-3alkyl-, -heteroaryl-C1-3heteroalkyl-, —C1-3alkyl-aryl-C1-3 alkyl-, —C1-3heteroalkyl-aryl-C1-3 alkyl-, —C1-3alkyl-heteroaryl-C1-3 alkyl-, —C1-3alkyl-aryl-C1-3 heteroalkyl-, —C1-3heteroalkyl-heteroaryl-C1-3 alkyl-, —C1-3heteroalkyl-aryl-C1-3 heteroalkyl-, —C1-3alkyl-heteroaryl-C1-3 heteroalkyl-, or —C1-3heteroalkyl-heteroaryl-C1-3 heteroalkyl-;
X is independently —R11—; and
E is independently selected from the group consisting of —N(R12)2, —N(R12)(R13), —S—R12, and
where —R12 is —CH2CH2-G,
where each G is independently —Cl, —Br, —I, —O—S(═O)2—CH3, —O—S(═O)2—CH2—C6H5, or —O—S(═O)2—C6H4—CH3; and where R13 is independently —C1-8 alkyl, —C1-8 heteroalkyl, -aryl, -heteroaryl, —C1-3alkyl-aryl, —C1-3heteroalkyl-aryl, —C1-3alkyl-heteroaryl, —C1-3heteroalkyl-heteroaryl, -aryl-C1-3alkyl, -aryl-C1-3heteroalkyl, -heteroaryl-C1-3alkyl, -heteroaryl-C1-3 heteroalkyl, —C1-3alkyl-aryl-C1-3 alkyl, —C1-3heteroalkyl-aryl-C1-3 alkyl, —C1-3alkyl-heteroaryl-C1-3 alkyl, —C1-3alkyl-aryl-C1-3 heteroalkyl, —C1-3heteroalkyl-heteroaryl-C1-3 alkyl, —C1-3heteroalkyl-aryl-C1-3 heteroalkyl, —C1-3alkyl-heteroaryl-C1-3 heteroalkyl, or —C1-3heteroalkyl-heteroaryl-C1-3 heteroalkyl;
and derivatives thereof, or a salt or stereoisomer of any of the foregoing;
c) assaying an amount of binding between antibodies from the sample and the surface-bound moiety of the red blood cells, wherein binding between the antibodies and the surface-bound moiety indicates presence of antibodies reactive to the pathogen-inactivated red blood cells in the potential recipient.

### Claim 45

(canceled)

### Claim 46 (depends on 44)

The method of claim 44, wherein the compound is selected from the group consisting of compounds of Formula VIII and derivatives thereof, or a salt or stereoisomer of any of the foregoing.

### Claim 47 (depends on 46)

The method of claim 46, wherein R1, R2, R3, R4, R5, R6, R7, and R8 are each hydrogen.

### Claim 48 (depends on 46)

The method of claim 46, wherein R20 is H.

### Claim 49 (depends on 46)

The method of claim 46, wherein R21 is —C1-8alkyl-N(CH2CH2Cl)2.

### Claim at position 8

50-51. (canceled)

### Claim 52 (depends on 44)

The method of claim 44, wherein the compound is a non-frangible analog of S-303, or a salt thereof.

### Claim 53 (depends on 52)

The method of claim 52, wherein the non-frangible analog of S-303 is S-197 or S-220.

### Claim 54

(canceled)

### Claim 55 (depends on 44)

The method of claim 44, wherein the surface-bound moiety is a non-frangible analog of S-303, or a salt thereof.

### Claim 56 (depends on 44)

The method of claim 44, wherein the moiety bound to the surface of the red blood cells is present at a loading level of at least about 10,000 moieties per red blood cell.

### Claim 57 (depends on 44)

The method of claim 44, wherein the moiety bound to the surface of the red blood cells is present at a loading level of at least about 50 moieties/μm2.

### Claim 58 (depends on 44)

The method of claim 44, wherein the compound and the surface-bound moiety are the same.

### Claim 59 (depends on 44)

The method of claim 44, wherein the compound and the surface-bound moiety are different.

### Claim 60 (depends on 44)

The method of claim 44, wherein step (c) comprises comparing the amount of binding between antibodies from the sample and the surface-bound moiety with a reference, and wherein an increased amount of binding as compared with the reference indicates the presence of antibodies reactive to the pathogen-inactivated red blood cell in the sample.

### Claim 61 (depends on 60)

The method of claim 60, wherein step (c) comprises assaying an amount of binding between antibodies from the sample and red blood cells that lack the surface-bound moiety.

### Claim 62 (depends on 60)

The method of claim 60, wherein step (c) further comprises assaying an amount of binding between antibodies from the sample and red blood cells having a reduced amount of the surface-bound moiety.

### Claim 63 (depends on 44)

The method of claim 44, wherein step (b) comprises contacting the sample and the red blood cells with anti-human globulin, and wherein step (c) comprises assaying an amount of agglutination.

### Claim 64 (depends on 44)

A method of providing a red blood cell transfusion to a patient, wherein the red blood cell transfusion comprises red blood cells treated with a pathogen-inactivating compound, the method comprising:
a) testing a sample from the patient for the presence of antibodies according to claim 44;
b) determining whether the amount of binding is higher than a reference; and
c) in accordance with a determination that the amount of binding is not higher than the reference, providing the red blood cell transfusion to the patient.

### Claim at position 22

65-66. (canceled)

### Claim 67 (depends on 64)

The method of claim 64, wherein the surface-bound moiety is selected from the group consisting of compounds of Formula VIII and derivatives thereof, or a salt or stereoisomer of any of the foregoing.

### Claim 68 (depends on 67)

The method of claim 67, wherein R1, R2, R3, R4, R5, R6, R7, and R8 are each hydrogen.

### Claim 69 (depends on 67)

The method of claim 67, wherein R20 is H.

### Claim 70 (depends on 67)

The method of claim 67, wherein R21 is —C1-8alkyl-N(CH2CH2Cl)2.

### Claim at position 27

71-73. (canceled)

### Claim 74 (depends on 64)

The method of claim 64 wherein the surface-bound moiety is a non-frangible analog of S-303 or a salt thereof.

### Claim 75 (depends on 74)

The method of claim 74, wherein the non-frangible analog of S-303 is S-197 or S-220.

### Claim 76 (depends on 64)

The method of claim 64, wherein the compound and the surface-bound moiety are the same.

### Claim 77 (depends on 64)

The method of claim 64, wherein the compound and the surface-bound moiety are different.

### Claim at position 32

78-93. (canceled)