# US 8,569,460 B2 · Antibody constant domain regions and uses thereof

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- Number: US 8,569,460 B2
- Document ID: US8569460B2
- Status: Granted
- Kind: B2
- Application number: 12/660,798
- Filed: 2010-03-04
- Published: 2011-01-06
- Granted: 2013-10-29
- Earliest claimed: 2009-03-25
- Assignees: Vet Therapeutics, Inc.
- Applicants: Geneviève Hansen
- Inventors: Geneviève Hansen
- Web page: https://patentgrep.com/patent/US8569460B2

## CPC

- C07K 16/464: {Igs containing CDR-residues from one specie grafted between FR-residues from another}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07K 16/18: against material from animals or humans
- G01N 33/6854: {Immunoglobulins}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/20: characterized by taxonomic origin
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- 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

The invention provides recombinant protein (e.g., a recombinant antibody or soluble receptor) having (i) a binding domain capable of specific binding to an epitope (for example an antibody variable domains, a receptor, a growth factor, a cytokine, or a fragment of any of the foregoing which is capable of specifically binding the desired epitope) and (ii) an effector domain comprising a constant domain region which is derived from immunoglobulin of a first species which is a companion mammal, e.g. dog, cat, or horse, having engineered substitutions at one or more positions and having an altered interaction with one or more FcRs or other ligands, and optionally enhanced effector function, relative to the parent constant domain region.

## Claims

### Claim 1

A recombinant protein comprising
a. a binding domain, or a fragment thereof, that specifically binds to an epitope; the binding domain comprising (i) a non-canine antibody hypervariable region or an epitope-binding fragment thereof, or (ii) a soluble receptor binding domain or an epitope-binding fragment thereof; and
b. an effector domain that provides ADCC and/or CDC effector function to the recombinant protein; the effector domain comprising a constant domain region; wherein the constant domain region comprises SEQ ID NO: 2.

### Claim 2 (depends on 1)

The recombinant protein of claim 1 which is a member of the immunoglobulin superfamily comprising an Ig fold.

### Claim 3 (depends on 1)

The recombinant protein of claim 1, wherein the binding domain comprises an antibody variable region.

### Claim 4 (depends on 1)

The recombinant protein of claim 1, wherein the epitope is selected from the group consisting of: a receptor, a growth factor, and a cytokine.

### Claim 5 (depends on 1)

The recombinant protein of claim 1, wherein the effector domain binds to an FcR.

### Claim 6 (depends on 1)

The recombinant protein of claim 1, wherein the recombinant protein has increased ADCC effector function relative to dog gamma globulin.

### Claim 7 (depends on 1)

The recombinant protein of claim 1, wherein the recombinant protein has increased CDC effector function relative to dog gamma globulin.

### Claim 8 (depends on 1)

The recombinant protein of claim 1, wherein the recombinant protein exhibits a TM of at least about the TM of dog gamma globulin.

### Claim 9 (depends on 1)

The recombinant protein of claim 1, wherein the effector domain further comprises a constant domain region of a kappa light chain comprising the sequence set forth in SEQ ID NO:8.

### Claim 10 (depends on 1)

The recombinant protein of claim 1, wherein the effector domain further comprises a constant domain region of a lambda light chain comprising the sequence set forth in SEQ ID NO:9.

### Claim 11 (depends on 1)

A recombinant protein according to claim 1 wherein the binding domain comprises hypervariable regions from an antibody from a species other than the companion animal.

### Claim 12 (depends on 11)

A recombinant protein according to claim 11 which is a heterochimeric antibody.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising the recombinant protein according to claim 1, in combination or association with a pharmaceutically acceptable diluent of carrier.

### Claim 14

A recombinant protein comprising SEQ ID NO: 2.
