# US 8,147,832 B2 · CD20-binding polypeptide compositions and methods

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- Number: US 8,147,832 B2
- Document ID: US8147832B2
- Status: Granted
- Kind: B2
- Application number: 10/917,599
- Filed: 2004-08-13
- Published: 2005-03-31
- Granted: 2012-04-03
- Earliest claimed: 2003-11-14
- Assignees: Merck Patent GmbH
- Inventors: Francis Joseph Carr; Stephen Williams; Stephen D. Gillies
- Web page: https://patentgrep.com/patent/US8147832B2

## CPC

- C07K 16/2887: {against CD20}
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 16/3076: {against structure-related tumour-associated moieties}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- C07K 2319/00: Fusion polypeptide
- Y10S 424/80: Antibody or fragment thereof whose amino acid sequence is disclosed in whole or in part
- Y10S 424/801: involving antibody or fragment thereof produced by recombinant dna technology
- 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
- 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)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

A CD20-binding polypeptide composition comprising a combination of a modified heavy chain variable region polypeptide and a modified light chain variable region polypeptide. The combination can be (a) a modified 2B8 antibody heavy chain variable region polypeptide of SEQ ID NO: 48; and a modified 2B8 antibody light chain variable region polypeptide of SEQ ID NO: 49; or (b) a modified Leu16 antibody heavy chain variable region polypeptide of SEQ ID NO: 50; and a modified Leu16 antibody light chain variable region polypeptide of SEQ ID NO: 51.

## Claims

### Claim 1

A CD20-binding polypeptide composition comprising a combination of a modified heavy chain variable region polypeptide and a modified ht chain variable region polypeptide, the combination being selected from the group consisting of:
(a) a combination of a modified 2B8 antibody heavy chain variable region polypeptide having the amino acid residue sequence of SEQ ID NO: 48 and which includes at least one of the following amino acid residues: K at residue 12, P at residue 14, V at residue 20, T at residue 48, T at residue 68, E at residue 82, R at residue 87, T at residue 91, and W at residue 106; and a modified 2B8 antibody light chain variable region polypeptide having the amino acid residue sequence of SEQ ID NO: 49 and which includes at least one of the following amino acid residues: I at residue 11, T at residue 12, T at residue 27, A at residue 29, T at residue 40, S at residue 59, T at residue 69, M at residue 72, S at residue 76, and L at residue 77; and
(b) a combination of a modified Leu16 antibody heavy chain variable region polypeptide having the amino acid residue sequence of SEQ ID NO: 50 and which includes at least one of the following amino acid residues: K at residue 12, V at residue 20, T at residue 68, E at residue 82, Rat residue 87, T at residue 91, V at residue 93, and T at residue 114; and a modified Leu16 antibody light chain variable region polypeptide having the amino acid residue sequence of SEQ ID NO: 51 and which includes at least one of the following amino acid residues: I at residue 11, T at residue 12, S at residue 59, T at residue 69, M at residue 72, S at residue 76, and L at residue 77.

### Claim 2 (depends on 1)

The CD20-binding polypeptide composition of claim 1 in the form of a chimeric antibody and further including a human heavy chain constant region and a human light chain constant region.

### Claim 3 (depends on 2)

The CD20-binding polypeptide composition of claim 2 wherein the human heavy chain constant region is an IgG constant region.

### Claim 4 (depends on 3)

The CD20-binding polypeptide composition of claim 3 wherein the IgG constant region is an IgG1 constant region.

### Claim 5 (depends on 2)

The CD20-binding polypeptide composition of claim 2 wherein the human light chain constant region is a human kappa light chain constant region.

### Claim 6 (depends on 2)

The CD20-binding polypeptide composition of claim 2 in the form of a fusion protein with human IL-2.

### Claim 7 (depends on 1)

The CD20-binding polypeptide composition of claim 1, in the form of a fusion protein with human IL-2.

### Claim 8 (depends on 1)

The CD20-binding polypeptide composition of claim 1 in the form of a Fab antibody fragment, a single-chain Fv antibody fragment, and minibody.

### Claim 9

A CD20-binding polypeptide composition comprising (a) a modified 2B8 antibody heavy chain variable region polypeptide having an amino acid residue sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 3; and a modified 2B8 antibody light chain variable region polypeptide having an amino acid residue sequence selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8; or (b) a modified Leu16 antibody heavy chain polypeptide having the amino acid residue sequence of SEQ ID NO: 10 and a modified Leu16 antibody light chain variable region polypeptide having the amino acid residue sequence of SEQ ID NO 12.

### Claim 10 (depends on 9)

The CD20-binding polypeptide composition of claim 9 comprising a polypeptide having an amino acid residue sequence of SEQ ID NO: 2 and a polypeptide having an amino acid residue sequence of SEQ ID NO: 5.

### Claim 11 (depends on 9)

The CD20-binding polypeptide composition of claim 9 comprising a polypeptide having an amino acid residue sequence of SEQ ID NO: 2 and a polypeptide having an amino acid residue sequence of SEQ ID NO: 6.

### Claim 12 (depends on 9)

The CD20-binding polypeptide composition of claim 9 comprising a polypeptide having an amino acid residue sequence of SEQ ID NO: 2 and a polypeptide having an amino acid residue sequence of SEQ ID NO: 7.

### Claim 13 (depends on 9)

The CD20-binding polypeptide composition of claim 9 comprising a polypeptide having an amino acid residue sequence of SEQ ID NO: 2 and a polypeptide having an amino acid residue sequence of SEQ ID NO: 8.

### Claim 14 (depends on 9)

The CD20-binding polypeptide composition of claim 9 comprising a polypeptide having an amino acid residue sequence of SEQ ID NO: 3 and a polypeptide having an amino acid residue sequence of SEQ ID NO: 6.

### Claim 15 (depends on 9)

The CD20-binding polypeptide composition of claim 9 comprising a polypeptide having an amino acid residue sequence of SEQ ID NO: 3 and a polypeptide having an amino acid residue sequence of SEQ ID NO: 8.

### Claim 16

A CD20-binding polypeptide composition comprising a polypeptide having an amino acid residue sequence of SEQ ID NO: 10 and a polypeptide having an amino acid residue sequence of SEQ ID NO: 12.

### Claim 17 (depends on 1)

A pharmaceutical composition comprising a CD20-binding polypeptide composition of claim 1, together with a pharmaceutically acceptable carrier, excipient, or diluent.

### Claim 18 (depends on 17)

The pharmaceutical composition of claim 17 further comprising an additional pharmacologically effective drug.

### Claim 19 (depends on 9)

The CD20-binding polypeptide composition of claim 9, designated Leu16VhY/VkZ-IL2, in the form of a fusion protein with human IL2 and comprising a polypeptide which is a Vh polypeptide having amino acid residue sequence of SEQ ID NO: 10 and a polypeptide which is a Vk polypeptide having amino acid residue sequence of SEQ ID NO: 12.