# US 11,440,943 B2 · Therapeutic interferon alpha 1 proteins

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- Number: US 11,440,943 B2
- Document ID: US11440943B2
- Status: Granted
- Kind: B2
- Application number: 16/832,995
- Filed: 2020-03-27
- Published: 2020-10-01
- Granted: 2022-09-13
- Earliest claimed: 2019-03-28
- Assignees: Orionis Biosciences BV
- Applicants: Orionis Biosciences, Inc.; Orionis Biosciences BV
- Inventors: Nikolai Kley; Erik Depla; Lennart Zabeau; Jan Tavernier
- Web page: https://patentgrep.com/patent/US11440943B2

## CPC

- C07K 14/56: IFN-alpha
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/2851: {against the lectin superfamily, e.g. CD23, CD72}
- C07K 16/2887: {against CD20}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2317/22: from camelids, e.g. camel, llama or dromedary
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/00: Fusion polypeptide
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/70: containing domain for protein-protein interaction
- 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)

## Abstract

The present invention relates, in part, to chimeric proteins or chimeric protein complexes, such as Fc-based chimeric protein complexes, comprising interferon alpha 1, or a variant thereof, and their use as therapeutic agents.

## Claims

### Claim 1

A chimeric protein complex comprising:
(a) a human interferon alpha 1 (IFNα1) comprising an amino acid sequence having at least 97% identity with SEQ ID NO: 1 and having a substitution or deletion at position C86,
(b) one or more targeting moieties, the targeting moieties comprising single-domain antibodies or scFvs which specifically bind to a cellular target; wherein:
the IFNα1 of the chimeric protein complex exhibits attenuated activity as compared to wild type IFNα1 having SEQ ID NO: 1; and
the IFNα1 of the chimeric protein complex exhibits activity which is induced by attachment to the one or more targeting moieties and is greater than that of wild type IFNα1 having SEQ ID NO: 1, and
(c) an Fc domain connecting the IFNα1 and the one or more targeting moieties, the Fc domain having one or more mutations that reduce or eliminate one or more effector functions of the Fc domain, promotes Fc chain pairing in the Fc domain, or stabilizes a hinge region in the Fc domain, and being derived from a human IgG, selected from human IgG1, IgG2, IgG3, and IgG4,
wherein the chimeric protein complex is a heterodimer having a trans orientation/configuration, as relates to any targeting moiety and IFNα1, relative to each other, or any targeting moieties relative to each other, or any IFNα1s relative to each other.

### Claim 2 (depends on 1)

The chimeric protein complex of claim 1, wherein the IFNα1 of the chimeric protein complex comprises an amino acid sequence having at least 98% identity with SEQ ID NO: 1.

### Claim 3 (depends on 1)

The chimeric protein complex of claim 1, wherein the IFNα1 of the chimeric protein complex comprises an amino acid sequence having at least 99% identity with SEQ ID NO: 1.

### Claim 4 (depends on 1)

The chimeric protein complex of claim 1, wherein the substitution at position C86 is selected from C86S, C86A, and C86Y.

### Claim 5 (depends on 1)

The chimeric protein complex of claim 1, wherein the IFNα1 of the chimeric protein complex exhibits reduced affinity or activity for interferon-α/β receptor (IFNAR).

### Claim 6 (depends on 5)

The chimeric protein complex of claim 5, wherein the IFNα1 of the chimeric protein complex exhibits reduced affinity or activity for IFNAR1 or IFNAR2.

### Claim 7 (depends on 1)

The chimeric protein complex of claim 1, the one or more targeting moieties are directed against a tumor cell or an immune cell.

### Claim 8 (depends on 1)

The chimeric protein complex of claim 1, the one or more targeting moieties comprise a recognition domain that is an antibody or a derivative or format thereof, or a natural ligand for a receptor.

### Claim 9 (depends on 1)

The chimeric protein complex of claim 1, wherein the Fc is a human IgG1 Fc and comprises one or more mutations selected from L234A, L235A, and K322Q (according to EU numbering) and/or one or more mutations selected from L234, L235, K322, D265, P329, and P331 (according to EU numbering).

### Claim 10 (depends on 1)

A recombinant nucleic acid composition encoding the chimeric protein complex of claim 1.

### Claim 11 (depends on 10)

A host cell comprising a nucleic acid of claim 10.