# US 12,181,485 B2 · Methods of blood screening

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- Number: US 12,181,485 B2
- Document ID: US12181485B2
- Status: Granted
- Kind: B2
- Application number: 17/471,620
- Filed: 2021-09-10
- Published: 2022-05-05
- Granted: 2024-12-31
- Earliest claimed: 2020-09-10
- Assignees: CASI Pharmaceuticals, Inc.
- Applicants: CASI Pharmaceuticals, Inc.
- Inventors: Alexander Anthony Zukiwski; Connie Westhoff
- Web page: https://patentgrep.com/patent/US12181485B2

## CPC

- A61P 35/00: Antineoplastic agents
- G01N 33/80: involving blood groups or blood types {or red blood cells (white blood cells G01N33/56972)}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- G01N 2333/70596: Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
- G01N 2500/10: involving cells
- G01N 2800/24: Immunology or allergic disorders
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- 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)

## Abstract

The present invention relates to methods of identifying suitable donor blood for cancer patients receiving anti-CD38 antibodies as treatment. In particular, the present invention addresses problems associated with crossmatching patient and donor blood when the patient blood comprises anti-CD38 antibodies that interfere with crossmatching methods of the art.

## Claims

### Claim 1

A method of screening a blood sample obtained from a patient, wherein the patient has been administered an anti-CD38 antibody or antigen binding fragment thereof, the method comprising:
a) providing a blood sample from the patient;
b) providing a blood sample from a donor, wherein the donor blood sample comprises donor red blood cells; and
c) screening the patient blood sample, comprising determining the presence or absence of one or more patient antibodies in the patient blood sample that specifically bind to one or more red blood cell antigens expressed on the surface of the donor red blood cells,
wherein the method does not comprise a step of contacting the patient blood sample or the donor blood sample with an agent that inhibits binding of the anti-CD38 antibody or antigen binding fragment thereof to membrane-bound CD38 present on the surface of the one or more donor red blood cells,
wherein anti-CD38 antibody or antigen binding fragment thereof comprises
a) an HCDR1 comprising the amino acid sequence SEQ ID NO: 1;
an HCDR2 comprising the amino acid sequence SEQ ID NO: 2;
an HCDR3 comprising the amino acid sequence SEQ ID NO: 3;
an LCDR1 comprising the amino acid sequence SEQ ID NO: 4;
an LCDR2 comprising the amino acid sequence SEQ ID NO: 5; and
an LCDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 9, 10, 11 and 12; or
b) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17;
an HCDR2 comprising the amino acid sequence of SEQ ID NO: 18;
an HCDR3 comprising the amino acid sequence of SEQ ID NO: 19;
an LCDR1 comprising the amino acid sequence of SEQ ID NO: 20;
an LCDR2 comprising the amino acid sequence of SEQ ID NO: 21; and
an LCDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 22, 25 and 26.

### Claim 2 (depends on 1)

The method of claim 1 wherein the agent that inhibits binding of the anti-CD38 antibody or antigen binding fragment thereof to membrane-bound CD38 present on the surface of the one or more donor red blood cells is a soluble CD38 antigen, an anti-CD38 idiotype antibody, or an antigen-stripping agent.

### Claim 3 (depends on 2)

The method of claim 2 wherein the antigen-stripping agent is a redox reagent, optionally DTT, or an enzyme, optionally a protease.

### Claim 4 (depends on 3)

The method of claim 3 wherein the protease is selected from the group consisting of trypsin, alpha chymotrypsin, papain, and ficin.

### Claim 5 (depends on 1)

The method of claim 1, wherein the anti-CD38 antibody or antigen binding fragment thereof comprises:
a) a variable light chain comprising the amino acid sequence of SEQ ID NO: 7 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 8; or
b) a variable light chain comprising the amino acid sequence of SEQ ID NO: 23 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 24; or
c) a variable light chain comprising the amino acid sequence of SEQ ID NO: 7 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 13; or
d) a variable light chain comprising the amino acid sequence of SEQ ID NO: 7 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 14; or
e) a variable light chain comprising the amino acid sequence of SEQ ID NO: 7 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 15; or
f) a variable light chain comprising the amino acid sequence of SEQ ID NO: 7 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 16; or
g) a variable light chain comprising the amino acid sequence of SEQ ID NO: 23 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 27; or
h) a variable light chain comprising the amino acid sequence of SEQ ID NO: 23 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 28.

### Claim 6 (depends on 1)

The method of claim 1, wherein the anti-CD38 antibody or antigen binding fragment thereof is a monoclonal antibody, a domain antibody, a single chain antibody, a Fab fragment, a F (ab′)2 fragment, a single chain variable fragment (scFv), a scFv-Fc fragment, a single chain antibody (scAb), an aptamer, or a nanobody.

### Claim 7 (depends on 1)

The method of claim 1, wherein the anti-CD38 antibody or antigen binding fragment thereof is an IgG antibody, optionally an IgG1 antibody.

### Claim 8 (depends on 1)

The method of claim 1, wherein the patient antibodies are alloantibodies, and/or wherein the patient antibodies specifically bind to red blood cell antigens other than any red blood cell antigens expressed by the patient's red blood cells, and/or wherein the patient antibodies are clinically significant patient antibodies, and/or wherein the patient antibodies are IgG antibodies and/or IgM antibodies.

### Claim 9 (depends on 1)

The method of claim 1, wherein the patient has or is suffering from cancer, or where the patient is undergoing treatment for cancer.

### Claim 10 (depends on 9)

The method of claim 9, wherein the cancer is a solid tumour which expresses CD38 on the cell surface or wherein the cancer is a haematological malignancy which expresses CD38 on the cell surface.

### Claim 11 (depends on 9)

The method of claim 9, wherein the cancer is a T or B cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, plasmacytoma, or multiple myeloma.

### Claim 12 (depends on 1)

The method of claim 1, wherein the one or more red blood cell antigens expressed on the surface of the donor red blood cells are selected from the group consisting of Ab, ABO, Cromer, Diego, Duffy, Gerbich, GLOB, Indian, Kell, Kidd, Knops, Lewis, Lutheran, LW, MNS, P1, Rh, XK, Xg, and Yt.

### Claim 13 (depends on 1)

The method of claim 1, wherein the one or more red blood cell antigens expressed on the surface of the donor red blood cells are selected from the group consisting of Ab, Rh, MNS, P1, Lewis, Kell, Duffy, KIDD, Lutheran and Xg.

### Claim 14 (depends on 1)

The method of claim 1, wherein the patient has been administered the anti-CD38 antibody or antigen binding fragment thereof less than 1 year prior to the sample being obtained from the patient.

### Claim 15 (depends on 1)

The method of claim 1, comprising:
a) providing a blood sample obtained from a patient;
b) providing a blood sample obtained from a donor, wherein the donor blood sample comprises donor red blood cells;
c) contacting the patient blood sample with one or more donor red blood cells from the donor blood sample to provide a patient blood/donor red blood cell mixture;
d) incubating the patient blood/donor red blood cell mixture to enable any one or more patient antibodies in the patient blood sample, if present, to bind to one or more red blood cell antigens present on the one or more donor red blood cells, to form one or more patient antibody/donor red blood cell antigen complexes;
e) optionally separating, if present, the any one or more patient alloantibody/donor red blood cell antigen complexes from the patient blood/donor red blood cell mixture, optionally wherein the separating step comprises centrifugation; and
f) determining the presence or absence of patient antibodies in the patient blood sample that specifically bind to one or more red blood cell antigens expressed on the one or more donor red blood cells;
optionally further comprising centrifuging the patient blood/donor red blood cell mixture.

### Claim 16 (depends on 1)

The method of claim 1, further comprising a step of adding an agglutination agent that specifically binds together any antibodies present in the patient blood sample.

### Claim 17 (depends on 16)

The method of claim 16 wherein the agglutination agent that specifically binds together one or more patient antibodies in the patient blood sample is an anti-human globulin reagent.

### Claim 18 (depends on 1)

The method of claim 1, further comprising a step of screening the patient blood sample against a red blood cell panel prior to step (b) to determine the presence or absence of any patient antibodies in the patient blood sample that specifically bind to any red blood cell antigens present on the surface of any red blood cells in the red blood cell panel; optionally wherein the donor red blood cells in the donor blood sample do not express any red blood cell antigens capable of being specifically bound by any of the patient antibodies identified as specifically binding to any red blood cell antigens expressed on the surface of any red blood cells in the red blood cell panel.

### Claim 19 (depends on 1)

A method of treating a cancer in a patient, the method comprising providing a blood sample from the patient, and screening the blood sample according to the method of claim 1.

### Claim 20 (depends on 19)

The method of claim 19, wherein the patient has been administered an anti-CD38 antibody or antigen binding fragment thereof.

### Claim 21 (depends on 1, 20)

The method of claim 20, wherein the method comprises:
a) administering to the patient the anti-CD38 antibody or antigen binding fragment thereof;
b) obtaining a blood sample from the patient after administration of the anti-CD38 antibody or antigen binding fragment thereof; and
c) screening the patient blood sample according to the method of claim 1.

### Claim 22 (depends on 19)

The method of claim 19, wherein the cancer is a solid tumour which expresses CD38 on the cell surface.

### Claim 23 (depends on 19)

The method of claim 19, wherein the cancer is a haematological malignancy which expresses CD38 on the cell surface.

### Claim 24 (depends on 19)

The method of claim 19, wherein the cancer is a T or B cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, plasmacytoma, or multiple myeloma.

### Claim 25 (depends on 19)

The method of claim 19, further comprising a step of administering blood or red blood cells from the donor if the donor is found to be compatible with the patient.

### Claim 26 (depends on 1)

The method of claim 1, wherein the anti-CD38 antibody or antigen binding fragment thereof comprises a variable light chain comprising the amino acid sequence of SEQ ID NO: 7 and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 8.