# US 6,590,079 B2 · Anti-αvβ3 recombinant human antibodies, nucleic acids encoding same

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- Number: US 6,590,079 B2
- Document ID: US6590079B2
- Status: Granted
- Kind: B2
- Application number: 08/791,391
- Filed: 1997-01-30
- Published: 2001-08-23
- Granted: 2003-07-08
- Earliest claimed: 1997-01-30
- Assignees: Ixsys, Inc.
- Inventors: William D. Huse; Scott M. Glaser
- Web page: https://patentgrep.com/patent/US6590079B2

## CPC

- C07K 16/2848: {against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2319/00: Fusion polypeptide
- 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)

## Abstract

The invention provides a Vitaxin antibody and a LM609 grafted antibody exhibiting selective binding affinity to αvβ3. The Vitaxin antibody consists of at least one Vitaxin heavy chain polypeptide and at least one Vitaxin light chain polypeptide or functional fragments thereof. Also provided are the Vitaxin heavy and light chain polypeptides and functional fragments. The LM609 grafted antibody consists of at least one CDR grafted heavy chain polypeptide and at least one CDR grafted light chain polypeptide or functional fragment thereof. Nucleic acids encoding Vitaxin and LM609 grafted heavy and light chains as well as nucleic acids encoding the parental non-human antibody LM609 are additionally provided. Functional fragments of such encoding nucleic acids are similarly provided.

## Claims

### Claim 1

An antibody comprising at least one heavy chain polypeptide comprising a variable region amino acid sequence as that shown in FIG. 1A (SEQ ID NO:2) and at least one light chain polypeptide comprising a variable region amino acid sequence as that shown in FIG. 1B (SEQ ID NO:4) or a functional fragment thereof, said antibody or functional fragment thereof having integrin αvβ3 binding activity, integrin αvβ3 binding specificity or integrin αvβ3-inhibitory activity.

### Claim 2 (depends on 1)

The antibody of claim 1, wherein said functional fragment is Fv.

### Claim 3 (depends on 1)

The antibody of claim 1, wherein said functional fragment is Fab.

### Claim 4 (depends on 1)

The antibody of claim 1, wherein said functional fragment is F(ab)2.

### Claim 5 (depends on 1)

The antibody of claim 1, wherein said functional fragment is scFV.

### Claim 6 (depends on 1)

The antibody of claim 1, wherein said antibody or functional fragment thereof has substantially the same integrin αvβ3 binding activity, integrin αvβ3 binding specificity or integrin αvβ3-inhibitory activity as LM609.

### Claim 7

A nucleic acid encoding a heavy chain polypeptide comprising the heavy chain variable region amino acid sequence of SEQ ID NO:2.

### Claim 8 (depends on 7)

The nucleic acid of claim 7, said nucleic acid comprising the heavy chain variable region nucleotide sequence of SEQ ID NO:1.

### Claim 9

A nucleic acid encoding a functional fragment of a heavy chain variable region of an antibody having integrin αvβ3 binding activity, integrin αvβ3 binding specificity or integrin αvβ3-inhibitory activity, wherein the amino acid sequence of said heavy chain variable region consists of SEQ ID NO:2.

### Claim 10

A nucleic acid encoding a CDR of the heavy chain polypeptide of SEQ ID NO:2.

### Claim 11

A nucleic acid encoding a light chain polypeptide comprising the light chain variable region amino acid sequence of SEQ ID NO:4.

### Claim 12 (depends on 11)

The nucleic acid of claim 11, said nucleic acid comprising the light chain variable region nucleotide sequence of SEQ ID NO:3.

### Claim 13

A nucleic acid encoding a functional fragment of a light chain variable region of an antibody having integrin αvβ3 binding activity, integrin αvβ3 binding specificity or integrin αvβ3-inhibitory activity, wherein the amino acid sequence of said light chain variable region consists of SEQ ID NO:4.

### Claim 14

A nucleic acid encoding a CDR of the light chain polypeptide of SEQ ID NO:4.

### Claim 15

A heavy chain polypeptide comprising a variable region amino acid sequence as that shown in FIG. 1A (SEQ ID NO:2) or functional fragment thereof.

### Claim 16 (depends on 15)

The heavy chain polypeptide of claim 15, wherein said functional fragment comprises a variable chain polypeptide or a CDR polypeptide.

### Claim 17

A light chain polypeptide comprising a variable region amino acid sequence as that shown in FIG. 1B (SEQ ID NO:4) or a functional fragment thereof.

### Claim 18 (depends on 17)

The light chain polypeptide of claim 17, wherein said functional fragment comprises a variable chain polypeptide or a CDR polypeptide.

### Claim 19

A LM609 CDR-grafted antibody comprising at least one LM609 CDR-grafted heavy chain polypeptide comprising a variable region amino acid sequence as that shown in FIG. 1A (SEQ ID NO:2) and at least one LM609 CDR-grafted light chain polypeptide comprising a variable region amino acid sequence as that shown in FIG. 7 (SEQ ID NO:32) or a functional fragment thereof, said LM609 CDR-grafted antibody or functional fragment thereof having integrin αvβ3 binding activity, integrin αvβ3 binding specificity or integrin αvβ3-inhibitory activity.

### Claim 20 (depends on 19)

The antibody of claim 19, wherein said functional fragment is Fv.

### Claim 21 (depends on 19)

The antibody of claim 19, wherein said functional fragment is Fab.

### Claim 22 (depends on 19)

The antibody of claim 19, wherein said functional fragment is F(ab)2.

### Claim 23 (depends on 19)

The antibody of claim 19, wherein said functional fragment is scFV.

### Claim 24 (depends on 19)

The antibody of claim 19, wherein said LM609 CDR-grafted antibody or functional fragment thereof has substantially the same integrin αvβ3 binding activity, integrin αvβ3 binding specificity or integrin αvβ3-inhibitory activity as LM609.

### Claim 25

A nucleic acid encoding a LM609 CDR-grafted light chain polypeptide comprising the LM609 CDR-grafted light chain variable region amino acid sequence of SEQ ID NO:32.

### Claim 26 (depends on 25)

The nucleic acid of claim 25, said nucleic acid comprising the light chain variable region nucleotide sequence of SEQ ID NO:31.

### Claim 27

A nucleic acid encoding a functional fragment of a light chain variable region of an antibody having integrin αvβ3 binding activity, integrin αvβ3 binding specificity or integrin αvβ3-inhibitory activity, wherein the amino acid sequence of said light chain variable region consists of SEQ ID NO:32.

### Claim 28

A nucleic acid encoding a CDR of the LM609 CDR-grafted light chain polypeptide of SEQ ID NO:32.

### Claim 29

A LM609 CDR-grafted light chain polypeptide comprising a variable region amino acid sequence as that shown in FIG. 7 (SEQ ID NO:32) or a functional fragment thereof.

### Claim 30 (depends on 29)

The LM609 CDR-grafted light chain polypeptide of claim 29, wherein said functional fragment comprises a variable chain polypeptide or a CDR polypeptide.

### Claim 31

A nucleic acid encoding a heavy chain polypeptide for monoclonal antibody LM609 comprising the heavy chain variable region amino acid sequence of SEQ ID NO:6.

### Claim 32 (depends on 31)

The nucleic acid of claim 31, said nucleic acid comprising the heavy chain variable region nucleotide sequence of SEQ ID NO:5.

### Claim 33

A nucleic acid encoding a functional fragment of a heavy chain variable region of an antibody having integrin αvβ3 binding activity, integrin αvβ3 binding specificity or integrin αvβ3-inhibitory activity, wherein the amino acid sequence of said heavy chain variable region consists of SEQ ID NO:6.

### Claim 34

A nucleic acid encoding a CDR of the heavy chain polypeptide of SEQ ID NO:6.

### Claim 35

A nucleic acid encoding a light chain polypeptide for monoclonal antibody LM609 comprising the light chain variable region amino acid sequence of SEQ ID NO:8.

### Claim 36 (depends on 35)

The nucleic acid of claim 35, said nucleic acid comprising the light chain variable region nucleotide sequence of SEQ ID NO:7.

### Claim 37

A nucleic acid encoding a functional fragment of a light chain variable region of an antibody having integrin αvβ3 binding activity, integrin αvβ3 binding specificity or integrin αvβ3-inhibitory activity, wherein the amino acid sequence of said light chain variable region consists of SEQ ID NO:8.

### Claim 38

A nucleic acid encoding a CDR of the light chain polypeptide of SEQ ID NO:8.

### Claim 39 (depends on 1, 2, 3, 4, 5, 6, 19, 20, 21, 22, 23, 24)

A composition comprising the antibody or functional fragment of any of claims 1 to 6 or 19 to 24 and a formulation or medium.