# US 11,306,145 B2 · Binding molecules specific for FcγRIIA and uses thereof

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- Number: US 11,306,145 B2
- Document ID: US11306145B2
- Status: Granted
- Kind: B2
- Application number: 16/097,573
- Filed: 2017-04-28
- Published: 2020-01-02
- Granted: 2022-04-19
- Earliest claimed: 2016-04-29
- Assignees: Viela Bio, Inc.
- Applicants: Viela Bio, Inc.
- Inventors: Katherine Ann Vousden; Bo Chen; Gary Patrick Sims
- Web page: https://patentgrep.com/patent/US11306145B2

## CPC

- C07K 16/283: {against Fc-receptors, e.g. CD16, CD32, CD64 (CD23 C07K16/2851)}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 7/06: Antianaemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 39/02: Antidotes
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2039/505: {comprising antibodies}
- 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 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- 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)
- 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 disclosure provides FcγRIIA-binding molecules, for example, humanized monoclonal antibodies capable of inhibiting FcγRIIA activity, and methods of using the FcγRIIA binding molecules, for example, in treating or preventing inflammatory, immune-mediated, or autoimmune diseases or disorders.

## Claims

### Claim 1

An isolated binding molecule that specifically binds to FcγRIIA, wherein the binding molecule comprises:
(i) a heavy chain variable (VH) region comprising a VH-complementarity determining region (CDR)1 comprising SEQ ID NO: 29, VH-CDR2 comprising SEQ ID NO: 19, and VH-CDR3 comprising SEQ ID NO: 30; and
(ii) a light chain variable (VL) region comprising a VL-CDR1 comprising SEQ ID NO: 22, VL-CDR2 comprising SEQ ID NO: 31, and VL-CDR3 comprising SEQ ID NO: 32.

### Claim 2 (depends on 1)

The binding molecule of claim 1, wherein the VH region and VL region comprise the amino acid sequences of SEQ ID NO: 33 and SEQ ID NO: 34, respectively.

### Claim 3 (depends on 1)

The binding molecule of claim 1, which is selected from a murine antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a bi-specific antibody, a multi-specific antibody, an Fv, an Fab, an F(ab′)2, an Fab′, a dsFv fragment, a single chain Fv (scFV), an sc(Fv)2, a disulfide-linked (dsFv), a diabody, a triabody, a tetrabody, a minibody, or a single chain antibody.

### Claim 4 (depends on 1)

The binding molecule of claim 1, comprising a human immunoglobulin G (IgG) constant region.

### Claim 5 (depends on 4)

The binding molecule of claim 4, wherein the constant region comprises amino acid substitutions at Kabat positions 234, 235, and 331, wherein:
a. the amino acid at Kabat position 234 is substituted with Phenylalanine (F),
b. the amino acid at Kabat position 235 is substituted with Glutamic acid (E), and
c. the amino acid at Kabat position 331 is substituted with Serine (S).

### Claim 6 (depends on 4)

The binding molecule of claim 4, wherein the constant region comprises amino acid substitutions at Kabat positions 252, 254, and 256, wherein:
a. the amino acid at Kabat position 252 is substituted with Tyrosine (Y),
b. the amino acid at Kabat position 254 is substituted with Threonine (T), and
c. the amino acid at Kabat position 256 is substituted with Glutamic acid (E).

### Claim 7 (depends on 1)

The binding molecule of claim 1, which is conjugated to an agent selected from the group consisting of an antimicrobial agent, a therapeutic agent, a prodrug, a peptide, a protein, an enzyme, a lipid, a biological response modifier, a pharmaceutical agent, a lymphokine, a heterologous antibody or fragment thereof, a detectable label, a polyethylene glycol (PEG), a toxin, and a combination of two or more of any said agents.

### Claim 8 (depends on 1)

A composition comprising the binding molecule of claim 1 and a carrier.

### Claim 9 (depends on 1)

A method for inhibiting ribonucleoprotein-immune complex (RNP-IC)-mediated type I IFNα in a peripheral blood mononuclear cell (PBMC), the method comprising contacting the PBMC with the binding molecule of claim 1.

### Claim 10 (depends on 1)

A method for inhibiting anti-neutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation, the method comprising contacting a neutrophil with the binding molecule of claim 1.

### Claim 11 (depends on 1)

A method of treating or preventing an inflammatory, immune-mediated, or autoimmune disease or disorder in a subject, the method comprising administering to a subject in need of treatment an effective amount of the binding molecule of claim 1.

### Claim 12 (depends on 11)

The method of claim 11, wherein the disease or disorder is ANCA-associated vasculitis (AAV), systemic lupus erythematosus (SLE), lupus nephritis, membranous nephritis, giant cell arteritis (GCA) vasculitis, immune thrombocytopenia (ITP), rheumatoid arthritis, polymyositis, dermatomyositis, pemphigus, hemolytic anemia, mixed connective tissue disease, Sjögren's syndrome, scleroderma, an autoantibody disorder, an immune-complex-mediated disorder, ADA-mediated adverse effects, NETosis, and NETosis-associated disorders, including sepsis, thrombosis, acute kidney injury, acute lung injury, chronic obstructive pulmonary disease, glomerulonephritis, toxic liver injury, stroke, atherogenesis, Type I diabetes, and IgG mediated hypersensitive reaction.

### Claim 13 (depends on 1)

A method for detecting FcγRIIA in a sample, the method comprising (a) contacting the sample with the binding molecule of claim 1, and (b) detecting binding of the binding molecule to FcγRIIA, thereby detecting FcγRIIA in the sample.