# US 8,785,600 B2 · Anti-GCC antibody molecules and related compositions and methods

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- Number: US 8,785,600 B2
- Document ID: US8785600B2
- Status: Granted
- Kind: B2
- Application number: 12/910,393
- Filed: 2010-10-22
- Published: 2011-05-12
- Granted: 2014-07-22
- Earliest claimed: 2009-10-23
- Assignees: Millennium Pharmaceuticals, Inc.; Amgen British Columbia
- Applicants: Samuel S. Nam; Edward A. Greenfield; Theresa L. O'Keefe; Shixin Qin; John Babcook
- Inventors: Samuel S. Nam; Edward A. Greenfield; Theresa L. O'Keefe; Shixin Qin; John Babcook
- Web page: https://patentgrep.com/patent/US8785600B2

## CPC

- C07K 16/40: against enzymes
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/68033: {the drug being a maytansine}
- A61K 47/6871: {the antibody targeting an enzyme}
- A61P 35/00: Antineoplastic agents
- C07K 16/30: from tumour cells
- G01N 33/573: for enzymes or isoenzymes
- 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 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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
- 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

Antibodies and antigen-binding fragments of antibodies that bind GCC are disclosed. The antibodies bind an extracellular domain of GCC and can be internalized. In some embodiments, the antibodies are humanized, chimeric or human. Nucleic acids and vectors encoding the antibodies or portions thereof, recombinant cells that contain the nucleic acids, and compositions comprising the antibodies or antigen-binding fragments are also disclosed. The invention also provides therapeutic and diagnostic methods utilizing the antibodies and antigen-binding fragments provided herein.

## Claims

### Claim 1

An anti-GCC antibody molecule comprising a light chain variable region and a heavy chain variable region, wherein said light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and said heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the light chain variable region comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 112, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 114, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 116 and, wherein the heavy chain variable region comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 106, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 108, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 110.

### Claim 2 (depends on 1)

The anti-GCC antibody molecule of claim 1, further comprising human or human derived light and heavy variable region frameworks.

### Claim 3 (depends on 1)

The anti-GCC antibody molecule of claim 1, wherein said anti-GCC antibody molecule is an IgG1 antibody.

### Claim 4 (depends on 1)

An immunoconjugate of formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
Ab is an anti-GCC antibody molecule of claim 1;
X is a linker moiety which connects Ab and Z;
Z is a therapeutic agent or a label; and
m is an integer from 1 to 15.

### Claim 5 (depends on 4)

The immunoconjugate of claim 4, wherein —Z is a maytansine or an auristatin.

### Claim 6 (depends on 4)

The immunoconjugate of claim 4, wherein —Z is MMAE or MMAF.

### Claim 7 (depends on 4)

The immunoconjugate of claim 4, wherein the linker —X— has the formula -Aa-Ww-Yy-, and the immunoconjugate is characterized by formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
-A- is a Stretcher unit;
a is 0 or 1;
each —W— independently is an Amino Acid unit;
w is an integer ranging from 0 to 12;
—Y— is a self-immolative Spacer unit;
y is 0, 1, or 2;
Z is a therapeutic agent or label; and
m is an integer from 1 to 15.

### Claim 8

An immunoconjugate of formula (I-4):
or a pharmaceutically acceptable salt thereof, wherein:
Ab is an anti-GCC antibody molecule comprising a light chain variable region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO: 112, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 114, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 116, and a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO: 106, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 108, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 110; and
m is an integer from 1 to 8.

### Claim 9

An immunoconjugate of formula (I-5):
or a pharmaceutically acceptable salt thereof, wherein:
Ab is an anti-GCC antibody molecule comprising a light chain variable region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO: 112, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 114, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 116, and a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO: 106, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 108, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 110; and
m is an integer from 1 to 8.

### Claim 10

An immunoconjugate of formula (I-7):
or a pharmaceutically acceptable salt thereof, wherein:
Ab is an anti-GCC antibody molecule comprising a light chain variable region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO: 112, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 114, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 116, and a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO: 106, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 108, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 110; and
m is an integer from 1 to 8.

### Claim 11 (depends on 8)

The immunoconjugate of claim 8, wherein m is from 1 to 3.

### Claim 12 (depends on 8)

The immunoconjugate of claim 8, wherein m is from 3 to 5.

### Claim 13 (depends on 9)

The immunoconjugate of claim 9, wherein m is from 3 to 5.

### Claim 14 (depends on 10)

The immunoconjugate of claim 10, wherein m is from 3 to 5.

### Claim 15 (depends on 1)

The anti-GCC antibody molecule of claim 1, wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 20, and wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 18.

### Claim 16 (depends on 1)

The anti-GCC antibody molecule of claim 1, wherein said anti-GCC antibody molecule is conjugated to a therapeutic agent.