# US 11,999,786 B2 · Anti-CD48 antibodies, antibody drug conjugates, and uses thereof

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- Number: US 11,999,786 B2
- Document ID: US11999786B2
- Status: Granted
- Kind: B2
- Application number: 17/534,126
- Filed: 2021-11-23
- Published: 2022-05-26
- Granted: 2024-06-04
- Earliest claimed: 2020-11-24
- Assignees: Novartis AG
- Applicants: Novartis AG
- Inventors: Joseph Anthony D'Alessio; Claudia Judith Klinter; Cornelia Anne Mundt; Richard Vaughan Newcombe; Tamás Schweighoffer; Katharina Winkelbach
- Web page: https://patentgrep.com/patent/US11999786B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/6811: {the drug being a protein or peptide, e.g. transferrin or bleomycin}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6867: {the tumour determinant being from a cell of a blood cancer}
- A61P 35/00: Antineoplastic agents
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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

Disclosed herein are antibodies, antigen binding fragments thereof, and antibody drug conjugates thereof that bind human CD48. Also disclosed are pharmaceutical compositions comprising the antibodies, antigen binding fragments thereof, and antibody drug conjugates thereof; and methods of making and using such pharmaceutical compositions for treating cancer in a patient in need of treatment.

## Claims

### Claim 1

An anti-CD48 antibody or antigen-binding fragment comprising three heavy chain CDRs and three light chain CDRs selected from one of the following:
(i) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO:1, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO:2, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO:3; light chain CDR1 (LCDR1) consisting of SEQ ID NO:16, light chain CDR2 (LCDR2) consisting of SEQ ID NO:17, and light chain CDR3 (LCDR3) consisting of SEQ ID NO:18;
(ii) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO:4, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO:2, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO:3; light chain CDR1 (LCDR1) consisting of SEQ ID NO:16, light chain CDR2 (LCDR2) consisting of SEQ ID NO:17, and light chain CDR3 (LCDR3) consisting of SEQ ID NO:18;
(iii) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO:5, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO:6, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO:3; light chain CDR1 (LCDR1) consisting of SEQ ID NO:19, light chain CDR2 (LCDR2) consisting of SEQ ID NO:20, and light chain CDR3 (LCDR3) consisting of SEQ ID NO:21;
(iv) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO:7, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO:8, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO:9; light chain CDR1 (LCDR1) consisting of SEQ ID NO:22, light chain CDR2 (LCDR2) consisting of SEQ ID NO:20, and light chain CDR3 (LCDR3) consisting of SEQ ID NO:18;
(v) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO:27, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO:28, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO:29; light chain CDR1 (LCDR1) consisting of SEQ ID NO:42, light chain CDR2 (LCDR2) consisting of SEQ ID NO:43, and light chain CDR3 (LCDR3) consisting of SEQ ID NO:44;
(vi) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO:30, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO:28, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO:29; light chain CDR1 (LCDR1) consisting of SEQ ID NO:42, light chain CDR2 (LCDR2) consisting of SEQ ID NO:43, and light chain CDR3 (LCDR3) consisting of SEQ ID NO:44;
(vii) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO:31, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO:32, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO:29; light chain CDR1 (LCDR1) consisting of SEQ ID NO:45, light chain CDR2 (LCDR2) consisting of SEQ ID NO:46, and light chain CDR3 (LCDR3) consisting of SEQ ID NO:47; or
(viii) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO:33, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO:34, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO:35; light chain CDR1 (LCDR1) consisting of SEQ ID NO:48, light chain CDR2 (LCDR2) consisting of SEQ ID NO:46, and light chain CDR3 (LCDR3) consisting of SEQ ID NO:44.

### Claim 2 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the anti-CD48 antibody or antigen-binding fragment thereof comprises:
(i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:10, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:23; or
(ii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:36, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:49.

### Claim 3 (depends on 1)

The antibody or antigen-binding fragment of claim 1, wherein the anti-CD48 antibody comprises:
(a) the heavy chain amino acid sequence of SEQ ID NO:12 and the light chain amino acid sequence of SEQ ID NO:25;
(b) the heavy chain amino acid sequence of SEQ ID NO:14 and the light chain amino acid sequence of SEQ ID NO:25;
(c) The heavy chain amino acid sequence of SEQ ID NO:63 and the light chain amino acid sequence of SEQ ID NO:25;
(e) the heavy chain amino acid sequence of SEQ ID NO:38 and the light chain amino acid sequence of SEQ ID NO:51;
(f) the heavy chain amino acid sequence of SEQ ID NO:40 and the light chain amino acid sequence of SEQ ID NO:51; or
(g) The heavy chain amino acid sequence of SEQ ID NO:65 and the light chain amino acid sequence of SEQ ID NO:51.

### Claim 4 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a single chain Fv (scFv), a disulfide-linked Fv (sdFv), a Fd fragment, a Fv fragment, a maxibody, a minibody, an intrabody, a diabody, a half antibody, a one-arm antibody, a monoclonal antibody, a bispecific antibody, a bispecific T-cell engage antibody, a multispecific antibody, a chimeric antigen receptor T-cell, or a radioimmunconjugate.

### Claim 5 (depends on 1)

A nucleic acid encoding the antibody or antigen-binding fragment thereof of claim 1.

### Claim 6 (depends on 5)

The nucleic acid of claim 5 comprising the nucleic acid sequence of SEQ ID NO:11, SEQ ID NO:37, SEQ ID NO:24, or SEQ ID NO:50.

### Claim 7 (depends on 5)

The nucleic acid of claim 5 comprising the nucleic acid sequence of SEQ ID NOs:13, 15, 39, 41, 75, 77, 26, or 52.

### Claim 8 (depends on 5)

A vector comprising the nucleic acid of claim 5.

### Claim 9 (depends on 8)

A cell line comprising the vector of claim 8.

### Claim 10 (depends on 9)

A method of making an antibody or antigen-binding fragment thereof comprising growing the cell line of claim 9 under suitable conditions to express the antibody or antigen-binding fragment thereof, then purifying and isolating the antibody or antigen-binding fragment thereof.

### Claim 11 (depends on 1)

An antibody drug conjugate of Formula (I):
A-(LB-(D)n)y (I);
wherein:
A is the antibody or antigen-binding fragment thereof of claim 1;
LB is a linker;
D is a cytotoxic agent, wherein D is not a BCL-2 inhibitor, MCL-1 inhibitor, or BCL-XL inhibitor;
n is an integer from 1 to 10, and
y is an integer from 1 to 10,
wherein the Linker-Drug moiety (LB-(D)n) is covalently attached to the antibody or antigen binding fragment thereof (A).

### Claim 12 (depends on 11)

The antibody drug conjugate of claim 11, wherein the cytotoxic agent is an Eg5 inhibitor, a V-ATPase inhibitor, a HSP90 inhibitor, an IAP inhibitor, an mTor inhibitor, a microtubule stabilizer, a microtubule destabilizer, an auristatin, a dolastatin, a maytansinoid, a MetAP (methionine aminopeptidase), an inhibitor of nuclear export of proteins CRM1, a DPPIV inhibitor, an inhibitor of phosphoryl transfer reactions in mitochondria, a protein synthesis inhibitor, a kinase inhibitor, a CDK2 inhibitor, a CDK9 inhibitor, a proteasome inhibitor, a kinesin inhibitor, an HDAC inhibitor, a DNA damaging agent, a DNA alkylating agent, a DNA intercalator, a DNA minor groove binder, an RNA polymerase inhibitor, an amanitin, a spliceosome inhibitor, a topoisomerase inhibitor, a DHFR inhibitor, or a pro-apoptotic agent, but excluding BCL-2 inhibitors, MCL-1 inhibitors, and BCL-XL inhibitors.

### Claim 13 (depends on 11)

The antibody drug conjugate of claim 11, wherein the cytotoxic agent is an Eg5 inhibitor, a V-ATPase inhibitor, a HSP90 inhibitor, an IAP inhibitor, an mTor inhibitor, a microtubule stabilizer, a microtubule destabilizer, an auristatin, a dolastatin, a maytansinoid, a MetAP (methionine aminopeptidase), an inhibitor of nuclear export of proteins CRM1, a DPPIV inhibitor, an inhibitor of phosphoryl transfer reactions in mitochondria, a protein synthesis inhibitor, a kinase inhibitor, a CDK2 inhibitor, a CDK9 inhibitor, a proteasome inhibitor, a kinesin inhibitor, an HDAC inhibitor, a DNA damaging agent, a DNA alkylating agent, a DNA intercalator, a DNA minor groove binder, an RNA polymerase inhibitor, an amanitin, a spliceosome inhibitor, a topoisomerase inhibitor, or a DHFR inhibitor, but excluding BCL-2 inhibitors, MCL-1 inhibitors, and BCL-XL inhibitors.

### Claim 14 (depends on 11)

The antibody drug conjugate of claim 11, wherein the cytotoxic agent is an auristatin.

### Claim 15 (depends on 11)

The antibody drug conjugate of claim 11, wherein:
D is a cytotoxic agent selected from a compound of Formula (A):
wherein:
R1 is
R2 is H, C1-C6alkyl, —C(═O)R3, —(CH2)mOH, —C(═O)(CH2)mOH, —C(═O)((CH2)mO)nR4, —((CH2)mO)nR4 or C1-C6alkyl which is optionally substituted with —CN, —C(═O)NH2 or 1 to 5 hydroxyl;
each R3 is independently selected from C1-C6alkyl and C1-C6alkyl, which is optionally substituted with 1 to 5 hydroxyl; m is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; and
each R4 is independently selected from H and C1-C6alkyl;
or D is a cytotoxic agent selected from a compound of Formula (B):
wherein:
R1 is
R2 is H, C1-C6alkyl, —C(═O)R3, —(CH2)mOH, —C(═O)(CH2)mOH, —C(═O)((CH2)mO)nR4, —((CH2)mO)nR4 or C1-C6alkyl which is optionally substituted with —CN, —C(═O)NH2 or 1 to 5 hydroxyl;
each R3 is independently selected from C1-C6alkyl and C1-C6alkyl, which is optionally substituted with 1 to 5 hydroxyl; and
each R4 is independently selected from H and C1-C6alkyl.

### Claim 16 (depends on 11)

The antibody drug conjugate of claim 11, wherein n is 1, 2, 3, 4, 5, 6, 7 or 8.

### Claim 17 (depends on 11)

The antibody drug conjugate of claim 11, wherein y is 1, 2, 3 or 4.

### Claim 18 (depends on 11)

The antibody drug conjugate of claim 11, wherein each LB is a cleavable linker.

### Claim 19 (depends on 11)

The antibody drug conjugate of claim 11, wherein each LB is a non-cleavable linker.

### Claim 20 (depends on 11)

An antibody drug conjugate of claim 11, selected from

### Claim 21 (depends on 1)

An antibody drug conjugate comprising the structure of Formula (E):
wherein:
A is the antibody or antigen-binding fragment thereof of claim 1;
y is an integer from 1 to 10; n is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12;
R2 is H, C1-C6alkyl, —C(═O)R3, —(CH2)mOH, —C(═O)(CH2)mOH, —C(═O)((CH2)mO)nR4, —((CH2)mO)nR4 or C1-C6alkyl which is optionally substituted with —CN, —C(═O)NH2 or 1 to 5 hydroxy;
each R3 is independently selected from C1-C6alkyl and C1-C6alkyl, which is optionally substituted with 1 to 5 hydroxyl;
each R4 is independently selected from H and C1-C6alkyl;
L1 is —X1C(═O)((CH2)mO)p(CH2)m—**, —X1C(═O)(CH2)m—**, —X2X1C(═O)((CH2)mO)p(CH2)m—**, —X2X1C(═O)(CH2)m—**, —X3C(═O)((CH2)mO)p(CH2)m—**, —X3C(═O)(CH2)m—**, —X3C(═O)(CH2)mNHC(═O)((CH2)mO)p(CH2)m—**, —X3C(═O)(CH2)mNHC(═O)(CH2)m—**, —X3C(═O)(CH2)m—**, —X1C(═O)((CH2)mO)p(CH2)mX4(CH2)m—**, —X1C(═O)(CH2)mX4(CH2)m—**, —X2X1C(═O)((CH2)mO)p(CH2)mX4(CH2)m—** or —X2X1C(═O)(CH2)mX4(CH2)m—**, where ** indicates the point of attachment to R114;
X1 is
where ** indicates the point of attachment to the —NH— or to X2;
X2 is
where ** indicates the point of attachment to the —NH—;
X3 is
where ** indicates the point of attachment to the —NH—;
X4 is
where the * indicates the point of attachment is toward R114;
R114 is
—NR6C(═O)CH2—*, —NHC(═O)CH2—*, —S(═O)2CH2CH2—*, —(CH2)2S(═O)2CH2CH2—*, —NR6S(═O)2CH2CH2—*, —NR6C(═O)CH2CH2—*, —NH—, —C(═O)—, —NHC(═O)—*, —CH2NHCH2CH2—*, —NHCH2CH2—*, —S—,
where the * indicates the point of attachment to A;
each R6 is independently selected from H and C1-C6alkyl;
each R10 is independently selected from H, C1-C6alkyl, F, Cl, and —OH;
each R11 is independently selected from H, C1-C6alkyl, F, Cl, —NH2, —OCH3, —OCH2CH3, —N(CH3)2, —CN, —NO2 and —OH;
each R12 is independently selected from H, C1-6alkyl, fluoro, benzyloxy substituted with —C(═O)OH, benzyl substituted with —C(═O)OH, C1-4alkoxy substituted with —C(═O)OH and C1-4alkyl substituted with —C(═O)OH;
each R15 is independently selected from H, —CH3 and phenyl;
each m is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, and
each p is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14.

### Claim 22 (depends on 21)

The antibody drug conjugate of claim 21, selected from

### Claim 23 (depends on 1)

An antibody drug conjugate comprising the structure of Formula (G):
wherein:
A is the antibody or antigen-binding fragment thereof of claim 1;
y is an integer from 1 to 10;
R2 is H, —C(═O)R3, —(CH2)mOH, —C(═O)(CH2)mOH, —C(═O)((CH2)mO)nR4, —((CH2)mO)nR4 or C1-C6alkyl which is optionally substituted with —CN, —C(═O)NH2 or 1 to 5 hydroxy;
each R3 is independently selected from C1-C6alkyl and C1-C6alkyl, which is optionally substituted with 1 to 5 hydroxyl;
each R4 is independently selected from H and C1-C6alkyl;
L1 is —X1C(═O)((CH2)mO)p(CH2)m—**, —X1C(═O)(CH2)m—**, —X2X1C(═O)((CH2)mO)p(CH2)m—**, —X2X1C(═O)(CH2)m—**, —X3C(═O)((CH2)mO)p(CH2)m—**, —X3C(═O)(CH2)m—**, —X3C(═O)(CH2)mNHC(═O)((CH2)mO)p(CH2)m—**, —X3C(═O)(CH2)mNHC(═O)(CH2)m—**, —X3C(═O)(CH2)m—**, —X1C(═O)((CH2)mO)p(CH2)mX4(CH2)m—**, —X1C(═O)(CH2)mX4(CH2)m—**, —X2X1C(═O)((CH2)mO)p(CH2)mX4(CH2)m—** or —X2X1C(═O)(CH2)mX4(CH2)m—**, where ** indicates the point of attachment to R114;
X1 is
where ** indicates the point of attachment to the —NH— or to X2;
X2 is
where ** indicates the point of attachment to the —NH—;
X3 is
where ** indicates the point of attachment to the —NH—;
X4 is
where the * indicates the point of attachment is toward R114;
R114 is
—NR6C(═O)CH2—*, —NHC(═O)CH2—*, —S(═O)2CH2CH2—*, —(CH2)2S(═O)2CH2CH2—*, —NR6S(═O)2CH2CH2—*, —NR6C(═O)CH2CH2—*, —NH—, —C(═O)—, —NHC(═O)—*, —CH2NHCH2CH2—*, —NHCH2CH2—*, —S—,
where the * indicates the point of attachment to A;
each R6 is independently selected from H and C1-C6alkyl;
each R10 is independently selected from H, C1-C6alkyl, F, Cl, and —OH;
each R11 is independently selected from H, C1-C6alkyl, F, Cl, —NH2, —OCH3, —OCH2CH3, —N(CH3)2, —CN, —NO2 and —OH;
each R12 is independently selected from H, C1-6alkyl, fluoro, benzyloxy substituted with —C(═O)OH, benzyl substituted with —C(═O)OH, C1-4alkoxy substituted with —C(═O)OH and C1-4alkyl substituted with —C(═O)OH;
each R15 is independently selected from H, —CH3 and phenyl;
each m is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, each n is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12; and
each p is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14.

### Claim 24 (depends on 23)

The antibody drug conjugate of claim 23 selected from

### Claim 25 (depends on 1)

A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

### Claim 26 (depends on 25)

The pharmaceutical composition of claim 25 further comprising one or more additional therapeutic agents.

### Claim 27 (depends on 25)

The pharmaceutical composition of claim 25, wherein the composition is a lyophilisate.

### Claim 28 (depends on 1)

A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment thereof of claim 1.

### Claim 29 (depends on 28)

The method of claim 28, wherein the cancer expresses CD48.

### Claim 30 (depends on 28)

The method of claim 28, wherein the cancer is a tumor, a hematological cancer, a breast cancer, multiple myeloma, B-cell lymphoma, plasma cell myeloma, leukemia, lymphoma, gastric cancer, acute myeloid leukemia, bladder cancer, brain cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, chronic lymphocytic leukemia, prostate cancer, small cell lung cancer, or spleen cancer.

### Claim 31 (depends on 28)

The method of claim 28, further comprising administering or using one or more additional therapeutic agents.

### Claim 32 (depends on 1)

A method of reducing or inhibiting the growth of a tumor in a subject, comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof of claim 1.

### Claim 33 (depends on 32)

The method of claim 32, wherein the tumor expresses CD48.

### Claim 34 (depends on 32)

The method of claim 32, wherein administration of the antibody or antigen-binding fragment thereof reduces or inhibits the growth of the tumor by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%.

### Claim 35 (depends on 1)

A method of reducing or slowing the expansion of a cancer cell population in a subject, comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment thereof of claim 1.

### Claim 36 (depends on 35)

The method of claim 35, wherein the cancer cell population expresses CD48.

### Claim 37 (depends on 35)

The method of claim 35, wherein the cancer cell population is from a tumor, a hematological cancer, a breast cancer, multiple myeloma, B-cell lymphoma, plasma cell myeloma, leukemia, lymphoma, gastric cancer, acute myeloid leukemia, bladder cancer, brain cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, chronic lymphocytic leukemia, prostate cancer, small cell lung cancer, or spleen cancer.

### Claim 38 (depends on 35)

The method of claim 35, wherein administration of the antibody or antigen-binding fragment thereof reduces the cancer cell population or slows the expansion of the cancer cell population by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%.

### Claim 39 (depends on 1)

A diagnostic agent comprising the antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment comprises a label.

### Claim 40 (depends on 39)

The diagnostic agent of claim 39, wherein the label is a radiolabel, a fluorophore, a chromophore, an imaging agent, or a metal ion.

### Claim 41 (depends on 39)

A method of detecting human CD48 in a tissue or cell comprising contacting the diagnostic agent of claim 39 to the tissue or cell and detecting binding of the diagnostic agent to the tissue or cell.