# US 2013/0158236 A1 · Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof

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- Number: US 2013/0158236 A1
- Document ID: US20130158236A1
- Status: Published application
- Kind: A1
- Application number: 13/344,195
- Filed: 2012-01-05
- Published: 2013-06-20
- Earliest claimed: 2000-12-08
- Assignees: Alexion Pharmaceuticals, Inc.
- Inventors: Katherine S. Bowdish; John McWhirter; Anke Kretz-Rommel; Toshiaki Maruyama
- Web page: https://patentgrep.com/patent/US20130158236A1

## CPC

- C07K 16/42: against immunoglobulins
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- C07K 16/3061: {Blood cells}
- C07K 16/3076: {against structure-related tumour-associated moieties}
- G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)}
- G01N 33/5011: {for testing antineoplastic activity}
- G01N 33/56972: {White blood cells}
- G01N 33/57505: of the blood, e.g. leukaemia
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- G01N 2333/70596: Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
- G01N 2500/20: cell-free systems
- 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)
- 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)

## Abstract

Cancer treatments use a therapy that: 1) interferes with the interaction between CD200 and its receptor to block immune suppression thereby promoting eradication of the cancer cells; and 2) directly kills the cancer cells either by complement-mediated or antibody-dependent cellular cytotoxicity or by targeting cells using a fusion molecule that includes a CD200-targeting portion. The therapy includes the administration of novel antibodies, functional fragments thereof or fusion molecules containing portions thereof.

## Claims

### Claim at position 1

1-13. (canceled)

### Claim 14

An isolated antibody, or antigen-binding fragment thereof, that binds to CD200, wherein the antibody or antigen-binding fragment comprises:
(i) a light chain polypeptide comprising: a light chain CDR1 comprising the sequence set forth in residues 26-35 of SEQ ID NO:207; a light chain CDR2 comprising the sequence set forth in residues 51-57 of SEQ ID NO:207; and a light chain CDR3 comprising the sequence set forth in resides 90-98 of SEQ ID NO:207; and
(ii) a heavy chain polypeptide comprising: a heavy chain CDR1 comprising the sequence set forth in SEQ ID NO:111; a heavy chain CDR2 comprising the sequence set forth in SEQ ID NO:118; and a heavy chain CDR3 comprising the sequence set forth in residues 100-112 of SEQ ID NO:201.

### Claim 15 (depends on 14)

The isolated antibody or antigen-binding fragment thereof according to claim 14, wherein the light chain polypeptide comprises the amino acid sequence depicted in SEQ ID NO:207 and wherein the heavy chain polypeptide comprises the amino acid sequence depicted in SEQ ID NO:201.

### Claim 16 (depends on 14)

The isolated antibody or antigen-binding fragment thereof according to claim 14, wherein the antibody or antigen-binding fragment is humanized, CDR-grafted, or chimeric.

### Claim 17 (depends on 14)

The isolated antibody or antigen-binding fragment thereof according to claim 14, wherein the antigen-binding fragment is selected from the group consisting of an Fv, an scFv, a Fab or F(ab)2 fragment.

### Claim 18 (depends on 14)

A pharmaceutical composition comprising the isolated antibody or antigen-binding fragment thereof according to claim 14.

### Claim 19

A fusion molecule comprising:
a first portion that targets cells bearing the OX-2/CD200 antigen, wherein the first portion is an antibody, or antigen-binding fragment thereof, that binds to CD200, wherein the antibody or antigen-binding fragment comprises: (i) a light chain polypeptide comprising: a light chain CDR1 comprising the sequence set forth in residues 26-35 of SEQ ID NO:207; a light chain CDR2 comprising the sequence set forth in residues 51-57 of SEQ ID NO:207; and a light chain CDR3 comprising the sequence set forth in resides 90-98 of SEQ ID NO:207; and (ii) a heavy chain polypeptide comprising: a heavy chain CDR1 comprising the sequence set forth in SEQ ID NO:111; a heavy chain CDR2 comprising the sequence set forth in SEQ ID NO:118; and a heavy chain CDR3 comprising the sequence set forth in residues 100-112 of SEQ ID NO:201; and
a second portion that promotes the death of cells, wherein the second portion is a cytotoxic compound selected from the group consisting of a cytotoxic drug, a bacterial toxin, a radioactive isotope, an immunoglobulin constant region having antibody-dependent cellular cytotoxicity (ADCC) activity, and an immunoglobulin constant region having complement-dependent cytotoxicity (CDC) activity.

### Claim 20 (depends on 19)

The fusion molecule according to claim 19, wherein the light chain polypeptide comprises the amino acid sequence depicted in SEQ ID NO:207 and wherein the heavy chain polypeptide comprises the amino acid sequence depicted in SEQ ID NO:201.

### Claim 21 (depends on 19)

The fusion molecule according to claim 19, wherein the antibody or antigen-binding fragment is humanized, CDR-grafted, or chimeric.

### Claim 22 (depends on 19)

The fusion molecule according to claim 19, wherein the antigen-binding fragment is selected from the group consisting of an Fv, an scFv, a Fab or F(ab)2 fragment.

### Claim 23 (depends on 19)

A pharmaceutical composition comprising the fusion molecule according to claim 19.