# US 2013/0156754 A1 · Optimized Fc Variants and Methods For Their Generation

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- Number: US 2013/0156754 A1
- Document ID: US20130156754A1
- Status: Published application
- Kind: A1
- Application number: 13/773,485
- Filed: 2013-02-21
- Published: 2013-06-20
- Earliest claimed: 2007-10-31
- Assignees: Xencor, Inc.
- Inventors: Gregory Alan Lazar; Arthur J. Chirino; Wei Dang; John Desjarlais; Stephen K. Doberstein; Robert J. Hayes; Sher Bahadur Karki; Omid Vafa
- Web page: https://patentgrep.com/patent/US20130156754A1

## CPC

- A61P 9/00: Drugs for disorders of the cardiovascular system
- C07K 16/283: {against Fc-receptors, e.g. CD16, CD32, CD64 (CD23 C07K16/2851)}
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 39/39566: {against immunoglobulins, e.g. anti-idiotypic antibodies}
- A61P 25/00: Drugs for disorders of the nervous system
- 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 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 16/22: against growth factors {; against growth regulators}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)}
- C07K 16/2887: {against CD20}
- C07K 16/2893: {against CD52}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- C07K 16/32: against translation products of oncogenes
- C07K 16/4291: {against IgE}
- C12P 21/005: {Glycopeptides, glycoproteins}
- G16B 5/00: ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
- G16B 15/00: ICT specially adapted for analysing two-dimensional [2D] or three-dimensional [3D] molecular structures, e.g. structural or functional relations or structure alignment
- G16B 30/00: ICT specially adapted for sequence analysis involving nucleotides or amino acids
- G16B 30/10: Sequence alignment; Homology search
- G16B 35/00: ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
- G16C 20/60: In silico combinatorial chemistry
- A61K 2039/505: {comprising antibodies}
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- 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 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/522: CH1 domain
- C07K 2317/524: CH2 domain
- C07K 2317/526: CH3 domain
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/71: Decreased effector function due to an Fc-modification
- C07K 2317/72: Increased effector function due to an Fc-modification
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- 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 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- G16B 15/20: Protein or domain folding
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16C: COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE

## Abstract

The present invention relates to optimized Fc variants, methods for their generation, and antibodies and Fc fusions comprising optimized Fc variants.

## Claims

### Claim at position 1

1-67. (canceled)

### Claim 68

A method of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) in a human comprising administering to a human a composition comprising a variant antibody of a parent antibody which variant mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of human peripheral blood mononuclear cells more effectively than the parent antibody, wherein said variant comprises a 239D substitution in the Fc region, wherein numbering is according to the EU index.

### Claim 69

A method of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) in a human comprising administering to a human a composition comprising a variant antibody of a parent antibody which variant mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of human peripheral blood mononuclear cells more effectively than the parent antibody, wherein said variant comprises a 239E substitution in the Fc region, wherein numbering is according to the EU index.

### Claim 70 (depends on 68, 69)

A method according to claim 68 or 69 wherein said variant antibody is a monoclonal antibody.

### Claim 71 (depends on 68, 69)

A method according to claim 68 or 69 wherein said variant antibody is a humanized antibody.

### Claim 72 (depends on 68, 69)

A method according to claim 68 or 69 wherein said variant antibody is a chimeric antibody.

### Claim 73 (depends on 68, 69)

A method according to claim 68 or 69 wherein said antibody binds to CD19.

### Claim 74 (depends on 68, 69)

A method according to claim 68 or 69 wherein said antibody binds to IgE.

### Claim 75 (depends on 68, 69)

A method according to claim 68 or 69 wherein said parent antibody is a human IgG1.

### Claim 76 (depends on 68, 69)

A method according to claim 68 or 69 wherein said variant antibody binds to a target antigen selected from the group consisting of CD20, CD30, CD33, CD37, CD38 and CD3.