# US 10,118,968 B2 · Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,118,968 B2
- Document ID: US10118968B2
- Status: Granted
- Kind: B2
- Application number: 12/649,179
- Filed: 2009-12-29
- Published: 2010-05-06
- Granted: 2018-11-06
- Earliest claimed: 2003-06-27
- Assignees: Amgen Fremont Inc.
- Applicants: Richard Weber; Xiao Feng; Orit Foord; Larry Green; Jean M. Gudas; Bruce Keyt; Ying Liu; Palaniswami Rathanaswami; Robert Raya; Xiao Dong Yang; Jose Corvalan; Ian Foltz; Xiao-Chi Jia; Jaspal S. Kang; Chadwick T. King; Scott L. Klakamp; Qiaojuan Jane Su
- Inventors: Richard Weber; Xiao Feng; Orit Foord; Larry Green; Jean M. Gudas; Bruce Keyt; Ying Liu; Palaniswami Rathanaswami; Robert Raya; Xiao Dong Yang; Jose Corvalan; Ian Foltz; Xiao-Chi Jia; Jaspal S. Kang; Chadwick T. King; Scott L. Klakamp; Qiaojuan Jane Su
- Web page: https://patentgrep.com/patent/US10118968B2

## CPC

- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61K 47/6803: {Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates}
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/68033: {the drug being a maytansine}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6897: {Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/08: of the prostate
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- C07K 16/30: from tumour cells
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- 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 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- Y10S 435/81: Packaged device or kit
- 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
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

The present invention relates to novel antibodies, particularly antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to the type III deletion mutant, EGFRvIII. The invention also relates to human monoclonal antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to EGFRvIII. Diagnostic and therapeutic formulations of such antibodies, and immunoconjugates thereof, are also provided.

## Claims

### Claim 1

An isolated antibody that binds to EGFRvIII, the antibody comprising:
a light chain variable region amino acid sequence that is at least 90 percent identical to the light chain variable region amino acid sequence in SEQ ID NO: 144;
a heavy chain variable region amino acid sequence that is at least 90 percent identical to the heavy chain variable region amino acid sequence in SEQ ID NO: 142; and
a toxin selected from a group consisting of maytansinoids and saporins conjugated to the antibody.

### Claim 2 (depends on 1)

The antibody of claim 1, wherein the toxin is a maytansinoid.

### Claim 3 (depends on 2)

The antibody of claim 2, wherein the maytansinoid comprises DM-1.

### Claim 4 (depends on 1)

The antibody of claim 1, wherein the toxin is conjugated to the antibody via a peptide linker.

### Claim 5 (depends on 1)

The antibody of claim 1, wherein the toxin comprises a saporin.

### Claim 6 (depends on 1)

The antibody of claim 1, wherein the toxin is indirectly conjugated to the antibody via a secondary antibody.

### Claim 7 (depends on 1)

The antibody of claim 1, wherein the antibody is a human antibody.

### Claim 8

An isolated antibody that binds to EGFRvIII, the antibody comprising:
a light chain variable region amino acid sequence that is at least 90 percent identical to the light chain variable region amino acid sequence in SEQ ID NO: 19;
a heavy chain variable region amino acid sequence that is at least 90 percent identical to the heavy chain variable region amino acid sequence in SEQ ID NO: 2; and
a toxin selected from a group consisting of maytansinoids and saporins conjugated to the antibody.

### Claim 9 (depends on 8)

The antibody of claim 8, wherein the toxin is a maytansinoid.

### Claim 10 (depends on 9)

The antibody of claim 9, wherein the maytansinoid comprises DM-1.

### Claim 11 (depends on 8)

The antibody of claim 8, wherein the toxin is conjugated to the antibody via a peptide linker.

### Claim 12 (depends on 8)

The antibody of claim 8, wherein the toxin comprises a saporin.

### Claim 13 (depends on 8)

The antibody of claim 8, wherein the toxin is indirectly conjugated to the antibody via a secondary antibody.

### Claim 14 (depends on 8)

The antibody of claim 8, wherein the antibody is a human antibody.

### Claim 15

An isolated antibody that binds to EGFRvIII, the antibody comprising:
a light chain variable region amino acid sequence that is at least 90 percent identical to the light chain variable region amino acid sequence in SEQ ID NO: 144;
a heavy chain variable region amino acid sequence that comprises the heavy chain variable region amino acid sequence in SEQ ID NO: 142; and
a toxin selected from a group consisting of maytansinoids and saporins conjugated to the antibody.

### Claim 16 (depends on 15)

The antibody of claim 15, wherein the toxin is a maytansinoid.

### Claim 17 (depends on 16)

The antibody of claim 16, wherein the maytansinoid comprises DM-1.

### Claim 18 (depends on 15)

The antibody of claim 15, wherein the toxin is conjugated to the antibody via a peptide linker.

### Claim 19 (depends on 15)

The antibody of claim 15, wherein the toxin comprises a saporin.

### Claim 20 (depends on 15)

The antibody of claim 15, wherein the toxin is indirectly conjugated to the antibody via a secondary antibody.

### Claim 21 (depends on 15)

The antibody of claim 15, wherein the antibody is a human antibody.

### Claim 22

An isolated antibody that binds to EGFRvIII, the antibody comprising:
a light chain variable region amino acid sequence that comprises the light chain variable region amino acid sequence in SEQ ID NO: 144;
a heavy chain variable region amino acid sequence that is at least 90 percent identical to the heavy chain variable region amino acid sequence in SEQ ID NO: 142; and
a toxin selected from the group consisting of maytansinoids and saporins conjugated to the antibody.

### Claim 23 (depends on 22)

The antibody of claim 22, wherein the toxin is a maytansinoid.

### Claim 24 (depends on 23)

The antibody of claim 23, wherein the maytansinoid comprises DM-1.

### Claim 25 (depends on 22)

The antibody of claim 22, wherein the toxin is conjugated to the antibody via a peptide linker.

### Claim 26 (depends on 22)

The antibody of claim 22, wherein the toxin comprises a saporin.

### Claim 27 (depends on 22)

The antibody of claim 22, wherein the toxin is indirectly conjugated to the antibody via a secondary antibody.

### Claim 28 (depends on 22)

The antibody of claim 22, wherein the antibody is a human antibody.

### Claim 29

An isolated antibody that binds to EGFRvIII, the antibody comprising:
a light chain variable region amino acid sequence that is at least 90 percent identical to the light chain variable region amino acid sequence in SEQ ID NO: 19;
a heavy chain variable region amino acid sequence that comprises the heavy chain variable region amino acid sequence in SEQ ID NO: 2; and
a toxin selected from a group consisting of maytansinoids and saporins conjugated to the antibody.

### Claim 30 (depends on 29)

The antibody of claim 29, wherein the toxin is a maytansinoid.

### Claim 31 (depends on 30)

The antibody of claim 30, wherein the Maytansinoid comprises DM-1.

### Claim 32 (depends on 29)

The antibody of claim 29, wherein the toxin is conjugated to the antibody via a peptide linker.

### Claim 33 (depends on 29)

The antibody of claim 29, wherein the toxin comprises a saporin.

### Claim 34 (depends on 29)

The antibody of claim 29, wherein the toxin is indirectly conjugated to the antibody via a secondary antibody.

### Claim 35 (depends on 29)

The antibody of claim 29, wherein the antibody is a human antibody.

### Claim 36

An isolated antibody that binds to EGFRvIII, the antibody comprising:
a light chain variable region amino acid sequence that comprises the light chain variable region amino acid sequence in SEQ ID NO: 19;
a heavy chain variable region amino acid sequence that is at least 90 percent identical to the heavy chain variable region amino acid sequence in SEQ ID NO: 2; and
a toxin selected from a group consisting of maytansinoids and saporins conjugated to the antibody.

### Claim 37 (depends on 36)

The antibody of claim 36, wherein the toxin is a maytansinoid.

### Claim 38 (depends on 37)

The antibody of claim 37, wherein the maytansinoid comprises DM-1.

### Claim 39 (depends on 36)

The antibody of claim 36, wherein the toxin is conjugated to the antibody via a peptide linker.

### Claim 40 (depends on 36)

The antibody of claim 36, wherein the toxin comprises a saporin.

### Claim 41 (depends on 36)

The antibody of claim 36, wherein the toxin is indirectly conjugated to the antibody via a secondary antibody.

### Claim 42 (depends on 36)

The antibody of claim 36, wherein the antibody is a human antibody.

### Claim 43 (depends on 1)

The antibody of claim 1, wherein the antibody binds to the amino acid sequence LEEKKGNYVVTDHC (SEQ ID NO:56).

### Claim 44 (depends on 8)

The antibody of claim 8, wherein the antibody binds to the amino acid sequence LEEKKGNYVVTDHC (SEQ ID NO:56).

### Claim 45 (depends on 15)

The antibody of claim 15, wherein the antibody binds to the amino acid sequence LEEKKGNYVVTDHC (SEQ ID NO:56).

### Claim 46 (depends on 22)

The antibody of claim 22 wherein the antibody binds to the amino acid sequence LEEKKGNYVVTDHC (SEQ ID NO:56).

### Claim 47 (depends on 29)

The antibody of claim 29, wherein the antibody binds to the amino acid sequence LEEKKGNYVVTDHC (SEQ ID NO:56).

### Claim 48 (depends on 36)

The antibody of claim 36, wherein the antibody binds to the amino acid sequence LEEKKGNYVVTDHC (SEQ ID NO:56).

### Claim 49

An isolated antibody, the antibody comprising:
a light chain variable region amino acid sequence that is at least 90 percent identical to the light chain variable region amino acid sequence in SEQ ID NO: 144;
a heavy chain variable region amino acid sequence that is at least 90 percent identical to the heavy chain variable region amino acid sequence in SEQ ID NO: 142; and
a toxin selected from a maytansinoid and saporin conjugated to the antibody.

### Claim 50 (depends on 49)

The isolated antibody of claim 49, wherein the light chain variable region amino acid sequence is at least 95 percent identical to the light chain variable region amino acid sequence in SEQ ID NO: 144; and the heavy chain variable region amino acid sequence is at least 95 percent identical to the heavy chain variable region amino acid sequence in SEQ ID NO: 142.

### Claim 51 (depends on 1)

The isolated antibody of claim 1, wherein the light chain variable region amino acid sequence is at least 95 percent identical to the light chain variable region amino acid sequence in SEQ ID NO: 144; and the heavy chain variable region amino acid sequence is at least 95 percent identical to the heavy chain variable region amino acid sequence in SEQ ID NO: 142.

### Claim 52 (depends on 8)

The isolated antibody of claim 8, wherein the light chain variable region amino acid sequence is at least 95 percent identical to the light chain variable region amino acid sequence in SEQ ID NO: 19; and the heavy chain variable region amino acid sequence is at least 95 percent identical to the heavy chain variable region amino acid sequence in SEQ ID NO: 2.

### Claim 53

An isolated antibody, the antibody comprising:
a light chain variable region amino acid sequence that is at least 90 percent identical to the light chain variable region amino acid sequence in SEQ ID NO: 19;
a heavy chain variable region amino acid sequence that is at least 90 percent identical to the heavy chain variable region amino acid sequence in SEQ ID NO: 2; and
a toxin selected from Maytansinoid and saporin conjugated to the antibody.

### Claim 54 (depends on 53)

The isolated antibody of claim 53, wherein the light chain variable region amino acid sequence is at least 95 percent identical to the light chain variable region amino acid sequence in SEQ ID NO: 19; and the heavy chain variable region amino acid sequence is at least 95 percent identical to the heavy chain variable region amino acid sequence in SEQ ID NO: 2.