# US 2020/0399381 A1 · Anti-ifnar1 antibodies for treating autoimmune diseases

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- Number: US 2020/0399381 A1
- Document ID: US20200399381A1
- Status: Published application
- Kind: A1
- Application number: 16/963,128
- Filed: 2019-09-18
- Published: 2020-12-24
- Earliest claimed: 2018-09-18
- Assignees: I-Mab Biopharma US Limited
- Applicants: I-Mab Biopharma US Limited
- Inventors: Wei Cao; Weili Xu
- Web page: https://patentgrep.com/patent/US20200399381A1

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)}
- G01N 33/53: Immunoassay; Biospecific binding assay; Materials therefor
- G01N 33/74: involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- 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 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- G01N 2333/7156: for interferons [IFN]
- 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
- 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

Provided are antibodies or fragments thereof having binding specificity to the human interferon alpha and beta receptor subunit 1 (IFNAR1) protein. In various examples, the antibodies or fragments thereof include a VH and VL CDRs as provided, or variants thereof. Methods of using the antibodies or fragments thereof for treating autoimmune diseases and disorders are also provided.

## Claims

### Claim 1

An antibody or fragment thereof having specificity to a human interferon alpha and beta receptor subunit 1 (IFNAR1) protein, wherein the antibody or fragment thereof comprises a heavy chain variable region comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and a light chain variable region comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from the group consisting of:
(a) HCDR1: DYYMH (SEQ ID NO: 77), HCDR2: RIDPEDGETKYAPKFQG (SEQ ID NO: 78) or RIDPEDAETKYAPKFQG (SEQ ID NO:79), HCDR3: GGNFYVMDY (SEQ ID NO: 80), LCDR1: KASQNVGTNVV (SEQ ID NO: 81), LCDR2: SASYRVS (SEQ ID NO: 82), and LCDR3: QQKNNYPYT (SEQ ID NO: 83); and
(b) HCDR1: DYYIH (SEQ ID NO: 92), HCDR2: RIDPEDGETKYAPKFQG (SEQ ID NO: 93) or RIDPEDAETKYAPKFQG (SEQ ID NO:94), HCDR3: YHGYWALDY (SEQ ID NO: 95), LCDR1: KTSQNVGTNVA (SEQ ID NO: 96), LCDR2: STSYRYS (SEQ ID NO: 97), and LCDR3: HQYFSYPYT (SEQ ID NO: 98).

### Claim 2 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the antibody is a chimeric antibody or a humanized antibody.

### Claim 3 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are HCDR1: DYYMH (SEQ ID NO: 77), HCDR2: RIDPEDAETKYAPKFQG (SEQ ID NO:79), HCDR3: GGNFYVMDY (SEQ ID NO: 80), LCDR1: KASQNVGTNVV (SEQ ID NO: 81), LCDR2: SASYRVS (SEQ ID NO: 82), and LCDR3: QQKNNYPYT (SEQ ID NO: 83).

### Claim 4 (depends on 3)

The antibody or fragment thereof of claim 3, which is humanized and wherein the heavy chain variable region comprises one or more back mutations selected from the group consisting of 12V, 20L, 24G, 38K, 481, 68A, 701, 72A, 79A and 81L, according to Kabat numbering, and combinations thereof.

### Claim 5 (depends on 3)

The antibody or fragment thereof of claim 3, which is humanized and wherein the light chain variable region comprises one or more back mutations selected from the group consisting of 4M, 13T, 21V, 43S, 46V, 741, 78V and 87F according to Kabat numbering, and combinations thereof.

### Claim 6 (depends on 3)

The antibody or fragment thereof of claim 3, comprising a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 7, and 84-87, or a peptide having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 7, and 84-87.

### Claim 7 (depends on 3)

The antibody or fragment thereof of claim 3, comprising a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 8, and 88-91, or a peptide having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 8, and 88-91.

### Claim 8 (depends on 3)

The antibody or fragment thereof of claim 3, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 85 or a peptide having at least 90% sequence identity to SEQ ID NO: 85, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 88 or a peptide having at least 90% sequence identity to SEQ ID NO: 88.

### Claim 9 (depends on 3)

The antibody or fragment thereof of claim 3, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 85, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 88.

### Claim 10 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are HCDR1: DYYIH (SEQ ID NO: 92), HCDR2: RIDPEDAETKYAPKFQG (SEQ ID NO:94), HCDR3: YHGYWALDY (SEQ ID NO: 95), LCDR1: KTSQNVGTNVA (SEQ ID NO: 96), LCDR2: STSYRYS (SEQ ID NO: 97), and LCDR3: HQYFSYPYT (SEQ ID NO: 98).

### Claim 11 (depends on 10)

The antibody or fragment thereof of claim 10, which is humanized and wherein the heavy chain variable region comprises one or more back mutations selected from the group consisting of 20L, 24G, 38K, 481, 68A, 701, 72A, 81L, and 97G, according to Kabat numbering, and combinations thereof.

### Claim 12 (depends on 10)

The antibody or fragment thereof of claim 10, which is humanized and wherein the light chain variable region comprises one or more back mutations selected from the group consisting of 13T, 21V, 36Y, 46P, 78V, and 104L, according to Kabat numbering, and combinations thereof.

### Claim 13 (depends on 10)

The antibody or fragment thereof of claim 10, comprising a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 73, and 99-102, or a peptide having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 73, and 99-102.

### Claim 14 (depends on 10)

The antibody or fragment thereof of claim 10, comprising a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 74, and 103-106, or a peptide having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 74, and 103-106.

### Claim 15 (depends on 10)

The antibody or fragment thereof of claim 10, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 100 or a peptide having at least 90% sequence identity to SEQ ID NO: 100, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 105 or a peptide having at least 90% sequence identity to SEQ ID NO: 105.

### Claim 16 (depends on 10)

The antibody or fragment thereof of claim 10, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 100, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 105.

### Claim at position 17

17-21. (canceled)

### Claim 22 (depends on 1)

A bifunctional molecule, comprising a first antigen-binding portion having specificity to a human interferon alpha and beta receptor subunit 1 (IFNAR1) protein and a second portion having specificity to a second protein, wherein the first antigen-binding portion comprises an antibody fragment of claim 1.

### Claim 23 (depends on 22)

The bifunctional molecule of claim 22, wherein the second portion comprises peptide edratide (hCDR1) or TACI-Ig.

### Claim 24 (depends on 22)

The bifunctional molecule of claim 22, wherein the second portion is an antigen-binding fragment having specificity to a protein selected from the group consisting of BAFF, CD20, CD22, CTLA4, IL6, CXCL13 and C5.

### Claim at position 21

25-29. (canceled)

### Claim 30 (depends on 1)

One or more polynucleotide encoding the antibody or fragment thereof of claim 1.

### Claim 31 (depends on 1)

A method of suppressing an immune response or treating an autoimmune disease or disorder in a patient in need thereof, comprising administering to the patient the antibody or fragment thereof of claim 1.

### Claim 32

(canceled)

### Claim 33 (depends on 31)

The method of claim 31, for treating an autoimmune disease or disorder.

### Claim 34 (depends on 33)

The method of claim 33, wherein the autoimmune disease or disorder is selected from the group consisting of type 1 diabetes, rheumatoid arthritis (RA), psoriasis/psoriatic arthritis, multiple sclerosis, systemic lupus erythematosus (lupus), inflammatory bowel disease, Addison's disease, Graves' disease, Sjögren's syndrome, Hashimoto's thyroiditis, myasthenia gravis, vasculitis, pernicious anemia, and celiac disease.

### Claim 35

(canceled)

### Claim 36 (depends on 1)

A method of detecting expression of a human interferon alpha and beta receptor subunit 1 (IFNAR1) protein in a sample, comprising contacting the sample with the antibody or fragment thereof of claim 1, and detecting the binding which indicates expression of IFNAR1 in the sample.