# US 2024/0199731 A1 · Il-17a binding proteins

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- Number: US 2024/0199731 A1
- Document ID: US20240199731A1
- Status: Published application
- Kind: A1
- Application number: 18/307,760
- Filed: 2023-04-26
- Published: 2024-06-20
- Earliest claimed: 2015-01-12
- Assignees: Crescendo Biologics Limited
- Applicants: Crescendo Biologics Limited
- Inventors: Bryan Edwards; Ulla Lashmar; Brian McGuinness; Mike Romanos; Thomas Sandal; Yumin Teng
- Web page: https://patentgrep.com/patent/US20240199731A1

## CPC

- C07K 16/244: {Interleukins [IL]}
- A01K 67/0278: Knock-in vertebrates, e.g. humanised vertebrates
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- G01N 33/6869: {Interleukin}
- A01K 2217/072: maintaining or altering function, i.e. knock in
- A01K 2217/075: inducing loss of function, i.e. knock out
- A01K 2217/15: Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
- A01K 2227/105: Murine
- A01K 2267/01: Animal expressing industrially exogenous proteins
- A61K 2039/505: {comprising antibodies}
- C07K 2317/565: Complementarity determining region [CDR]
- 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
- G01N 2333/54: Interleukins [IL]
- 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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

Binding molecules to IL-17A. The binding molecules are useful in the treatment of disorders, for example psoriasis.

## Claims

### Claim at position 1

1-61. (canceled)

### Claim 62

A binding molecule that is capable of binding human IL-17A comprising a heavy chain variable immunoglobulin (VH) domain selected from the group consisting of (a), (b), (c), (d), and (e):
(a) a CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 49, 57, 65, 69, 77, 93, 97, 101, 113, 117, 121, 125, 129, 141, 145, 149, 157, 165, 173, 177, 181, 193, 197, 205, 213, 217, 221, 225, 233, 237, 245, 442, 446, 450, 454, 458, and 462; a CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 50, 58, 66, 70, 78, 94, 98, 102, 114, 118, 122, 126, 130, 142, 146, 150, 158, 166, 174, 178, 182, 194, 198, 206, 214, 218, 222, 226, 234, 238, 246, 443, 447, 451, 455, 459, and 463; and a CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 51, 59, 67, 71, 79, 95, 99, 103, 115, 119, 123, 127, 131, 143, 147, 151, 159, 167, 175, 179, 183, 195, 199, 207, 215, 219, 223, 227, 235, 239, 247, 444, 448, 452, 456, 460, and 464; or
(b) a CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 249, 253, 257, 261, 265, and 273; a CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 250, 254, 258, 262, 266 and 274, and a CDR3 sequence comprising an amino acid sequence selected from SEQ ID NOs: 251, 255, 259, 263, 267, and 275; or
(c) a CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 285, 289, 293, 297, 301, 305, 317, 321, 325, 329, 333, and 337; a CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 286, 290, 294, 298, 302, 306, 318, 322, 326, 330, 334 and 338, and a CDR3 sequence comprising an amino acid sequence selected from SEQ ID NOs: 287, 291, 295, 299, 303, 307, 319, 323, 327, 331, 335 and 339; or
(d) a CDR1 sequence comprising SEQ ID NO: 341, a CDR2 sequence comprising SEQ ID NO: 342, and a CDR3 sequence comprising SEQ ID NO: 343 or
(e) a CDR1 sequence comprising SEQ ID NO: 345, a CDR2 sequence comprising SEQ ID NO: 346, and a CDR3 sequence comprising SEQ ID NO: 347.

### Claim 63 (depends on 62)

The binding molecule of claim 62, wherein the VH domain corresponds to (a), wherein the VH domain comprises a CDR1 having SEQ ID NO: 1, a CDR2 having SEQ ID NO: 2, and a CDR3 sequence having SEQ ID NO: 3; or a CDR1 having SEQ ID NO: 5, a CDR2 having SEQ ID NO: 6, and a CDR3 having SEQ ID NO: 7; or a CDR1 having SEQ ID NO: 9, a CDR2 having SEQ ID NO: 10, and a CDR3 having SEQ ID NO: 11; or a CDR1 having SEQ ID NO: 13, a CDR2 having SEQ ID NO: 14, and a CDR3 having SEQ ID NO: 15; or a CDR1 having SEQ ID NO: 17, a CDR2 having SEQ ID NO: 18, and a CDR3 having SEQ ID NO: 19; or a CDR1 having SEQ ID NO: 21, a CDR2 having SEQ ID NO: 22, and a CDR3 having SEQ ID NO: 23; or a CDR1 having SEQ ID NO: 25, a CDR2 having SEQ ID NO: 26, and a CDR3 having SEQ ID NO: 27; or a CDR1 having SEQ ID NO: 29, a CDR2 having SEQ ID NO: 30, and a CDR3 having SEQ ID NO: 31; or a CDR1 having SEQ ID NO: 33, a CDR2 having SEQ ID NO: 34, and a CDR3 having SEQ ID NO: 35; or a CDR1 having SEQ ID NO: 37, a CDR2 having SEQ ID NO: 38, and a CDR3 having SEQ ID NO: 39; or a CDR1 having SEQ ID NO: 41, a CDR2 having SEQ ID NO: 42, and a CDR3 having SEQ ID NO: 43; or a CDR1 having SEQ ID NO: 49, a CDR2 having a SEQ ID NO: 50, and a CDR3 having SEQ ID NO: 51; or a CDR1 having SEQ ID NO: 57, a CDR2 having SEQ ID NO: 58, and a CDR3 having SEQ ID NO: 59; or a CDR1 having SEQ ID NO: 65, a CDR2 having SEQ ID NO: 66, and a CDR3 having SEQ ID NO: 67; or a CDR1 having SEQ ID NO: 69, a CDR2 having SEQ ID NO: 70, and a CDR3 having SEQ ID NO: 71; or a CDR1 having SEQ ID NO: 77, a CDR2 having SEQ ID NO: 78, and a CDR3 having SEQ ID NO: 79; or a CDR1 having SEQ ID NO: 93, a CDR2 having SEQ ID NO: 94, and a CDR3 having SEQ ID NO: 95; or a CDR1 having SEQ ID NO: 97, a CDR2 having SEQ ID NO: 98, and a CDR3 having SEQ ID NO: 99; or a CDR1 having SEQ ID NO: 101, a CDR2 having SEQ ID NO: 102, and a CDR3 having SEQ ID NO: 103; or a CDR1 having SEQ ID NO: 113, a CDR2 having SEQ ID NO: 114, and a CDR3 having SEQ ID NO: 115; or a CDR1 having SEQ ID NO: 117, a CDR2 having SEQ ID NO: 118, and a CDR3 having SEQ ID NO: 119; or a CDR1 having SEQ ID NO: 121, a CDR2 having SEQ ID NO: 122, and a CDR3 having SEQ ID NO: 123; or a CDR1 having SEQ ID NO: 125, a CDR2 having SEQ ID NO: 126, and a CDR3 having SEQ ID NO: 127; or a CDR1 having SEQ ID NO: 129, a CDR2 having SEQ ID NO: 130, and a CDR3 having SEQ ID NO: 131; or a CDR1 having SEQ ID NO: 141, a CDR2 having SEQ ID NO: 142, and a CDR3 having SEQ ID NO: 143; or a CDR1 having SEQ ID NO: 145, a CDR2 having SEQ ID NO: 146, and a CDR3 having SEQ ID NO: 147; or a CDR1 having SEQ ID NO: 149, a CDR2 having SEQ ID NO: 150, and a CDR3 having SEQ ID NO: 151; or a CDR1 having SEQ ID NO: 157, a CDR2 having SEQ ID NO: 158, and a CDR3 having SEQ ID NO: 159; or a CDR1 having SEQ ID NO: 165, a CDR2 having SEQ ID NO: 166, and a CDR3 having SEQ ID NO: 167; or a CDR1 having SEQ ID NO: 173, a CDR2 having SEQ ID NO: 174, and a CDR3 having SEQ ID NO: 175; or a CDR1 having SEQ ID NO: 177, a CDR2 having SEQ ID NO: 178, and a CDR3 having SEQ ID NO: 179; or a CDR1 having SEQ ID NO: 181, a CDR2 having SEQ ID NO: 182, and a CDR3 having SEQ ID NO: 183; or a CDR1 having SEQ ID NO: 193, a CDR2 having SEQ ID NO: 194, and a CDR3 having SEQ ID NO: 195; or a CDR1 having SEQ ID NO: 197, a CDR2 having SEQ ID NO: 198, and a CDR3 having SEQ ID NO: 199; or a CDR1 having SEQ ID NO: 205, a CDR2 having SEQ ID NO: 206, and a CDR3 having SEQ ID NO: 207; or a CDR1 having SEQ ID NO: 213, a CDR2 having SEQ ID NO: 214, and a CDR3 having SEQ ID NO: 215; or a CDR1 having SEQ ID NO: 217, a CDR2 having SEQ ID NO: 218, and a CDR3 having SEQ ID NO: 219; or a CDR1 having SEQ ID NO: 221, a CDR2 having SEQ ID NO: 222, and a CDR3 having SEQ ID NO: 223; or a CDR1 having SEQ ID NO: 225, a CDR2 having SEQ ID NO: 226, and a CDR3 having SEQ ID NO: 227; or a CDR1 having SEQ ID NO: 233, a CDR2 having SEQ ID NO: 234, and a CDR3 having SEQ ID NO: 235; or a CDR1 having SEQ ID NO: 237, a CDR2 having SEQ ID NO: 238, and a CDR3 having SEQ ID NO: 239; or a CDR1 having SEQ ID NO: 245, a CDR2 having SEQ ID NO: 246, and a CDR3 having SEQ ID NO: 247; or a CDR1 having SEQ ID NO: 442, a CDR2 having SEQ ID NO: 443, and a CDR3 having SEQ ID NO: 444; or a CDR1 having SEQ ID NO: 446, a CDR2 having SEQ ID NO: 447, and a CDR3 having SEQ ID NO: 448; or a CDR1 having SEQ ID NO: 450, a CDR2 having SEQ ID NO: 451, and a CDR3 having SEQ ID NO: 452; or a CDR1 having SEQ ID NO: 454, a CDR2 having SEQ ID NO: 455, and a CDR3 having SEQ ID NO: 456; or a CDR1 having SEQ ID NO: 458, a CDR2 having SEQ ID NO: 459, and a CDR3 having SEQ ID NO: 460; or a CDR1 having SEQ ID NO: 462, a CDR2 having SEQ ID NO: 463, and a CDR3 having SEQ ID NO: 464.

### Claim 64 (depends on 63)

The binding molecule according to claim 63, wherein the VH domain comprises SEQ ID NO: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, 152, 156, 160, 164, 168, 172, 176, 180, 184, 188, 192, 196, 200, 204, 208, 212, 216, 220, 224, 228, 232, 236, 240, 244, 248, 411, 441, 445, 449, 453, 457, 461 or 466.

### Claim 65 (depends on 62)

The binding molecule according to claim 62, wherein the VH domain corresponds to (b), wherein the VH domain comprises a CDR1 having SEQ ID NO: 249, a CDR2 having SEQ ID NO: 250, and a CDR3 sequence having SEQ ID NO: 251; or a CDR1 having SEQ ID NO: 253, a CDR2 having SEQ ID NO: 254, and a CDR3 sequence having SEQ ID NO: 255; or a CDR1 having SEQ ID NO: 257, a CDR2 having SEQ ID NO: 258, and a CDR3 sequence having SEQ ID NO: 259; or a CDR1 having SEQ ID NO: 261, a CDR2 having SEQ ID NO: 262, and a CDR3 sequence having SEQ ID NO: 263; or a CDR1 having SEQ ID NO: 265, a CDR2 having SEQ ID NO: 266, and a CDR3 sequence having SEQ ID NO: 267; or a CDR1 having SEQ ID NO: 273, a CDR2 having SEQ ID NO: 274, and a CDR3 sequence having SEQ ID NO: 275.

### Claim 66 (depends on 62)

The binding molecule according to claim 62, wherein the VH domain corresponds to (c), wherein the VH domain comprises a CDR1 having SEQ ID NO: 285, a CDR2 having SEQ ID NO: 286, and a CDR3 sequence having SEQ ID NO: 287; or a CDR1 having SEQ ID NO: 289, a CDR2 having SEQ ID NO: 290, and a CDR3 sequence having SEQ ID NO: 291; or a CDR1 having SEQ ID NO: 293, a CDR2 having SEQ ID NO: 294, and a CDR3 sequence having SEQ ID NO: 295; or a CDR1 having SEQ ID NO: 297, a CDR2 having SEQ ID NO: 298, and a CDR3 sequence having SEQ ID NO: 299; or a CDR1 having SEQ ID NO: 301, a CDR2 having SEQ ID NO: 302, and a CDR3 sequence having SEQ ID NO: 303; or CDR1 having SEQ ID NO: 305, a CDR2 having SEQ ID NO: 306, and a CDR3 sequence having SEQ ID NO: 307; or a CDR1 having SEQ ID NO: 317, a CDR2 having SEQ ID NO: 318, and a CDR3 sequence having SEQ ID NO: 319; or a CDR1 having SEQ ID NO: 321, a CDR2 having SEQ ID NO: 322, and a CDR3 sequence having SEQ ID NO: 323; or a CDR1 having SEQ ID NO: 325, a CDR2 having SEQ ID NO: 326, and a CDR3 sequence having SEQ ID NO: 327; or a CDR1 having SEQ ID NO: 329, a CDR2 having SEQ ID NO: 330, and a CDR3 sequence having SEQ ID NO: 331; or a CDR1 having SEQ ID NO: 333, a CDR2 having SEQ ID NO: 334, and a CDR3 sequence having SEQ ID NO: 335; or a CDR1 having SEQ ID NO: 337, a CDR2 having SEQ ID NO: 338, and a CDR3 sequence having SEQ ID NO: 339.

### Claim 67 (depends on 62)

The binding molecule according to claim 62, wherein the VH domain corresponds to (d).

### Claim 68 (depends on 62)

The binding molecule according to claim 62, wherein the VH domain corresponds to (e).

### Claim 69 (depends on 62)

A pharmaceutical composition comprising:
a pharmaceutical carrier; and
a binding molecule according to claim 62.

### Claim 70 (depends on 69)

The composition according to claim 69, wherein the composition is formulated for topical administration to skin.

### Claim 71 (depends on 69)

A kit comprising the pharmaceutical composition according to claim 69.

### Claim 72 (depends on 62)

An isolated nucleic acid molecule comprising a nucleotide sequence encoding the binding molecule according to claim 62.

### Claim 73 (depends on 62)

An in vivo or in vitro method for reducing human IL-17 A activity, comprising: contacting human IL-17A with the binding molecule according to claim 62.

### Claim 74 (depends on 62)

A method for producing the binding molecule according to claim 62 comprising expressing a nucleic acid encoding said binding molecule in a host cell and isolating the binding molecule from the host cell.

### Claim 75 (depends on 69)

A method for treating at least one disease or condition selected from the group consisting of psoriasis, rheumatoid arthritis, non-infectious uveitis, lupus, spondyloarthropathy, immunologic diseases of the lung, asthma, allergic rhinitis, eosinophilic pneumonia, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, pneumoconiosis, pulmonary emphysema, and adult respiratory distress syndrome in a subject in need thereof comprising administering to the subject the pharmaceutical composition according to claim 69.

### Claim 76

A binding molecule, comprising:
a heavy chain variable immunoglobulin (VH) domain that comprises a CDR1, a CDR2, and a CDR3 sequence, wherein said CDR1 sequence comprises the amino acid sequence of SEQ ID NO: 5; wherein said CDR2 sequence comprises the amino acid sequence of SEQ ID NO: 6; and wherein said CDR3 sequence comprises the amino acid sequence of SEQ ID NO: 7.

### Claim 77 (depends on 76)

The binding molecule according to claim 76, wherein said VH domain comprises the amino acid sequence of SEQ ID NO: 8.

### Claim 78

A pharmaceutical composition, comprising:
a pharmaceutical carrier; and
a binding molecule that binds human IL-17A, said binding molecule comprising a heavy chain variable immunoglobulin (VH) domain that comprises a CDR1, a CDR2, and a CDR3 sequence, wherein said CDR1 sequence comprises the amino acid sequence of SEQ ID NO: 5; wherein said CDR2 sequence comprises the amino acid sequence of SEQ ID NO: 6; and wherein said CDR3 sequence comprises the amino acid sequence of SEQ ID NO: 7.

### Claim 79 (depends on 78)

The pharmaceutical composition according to claim 78, wherein said pharmaceutical composition is formulated for topical administration to the skin.

### Claim 80 (depends on 78)

The pharmaceutical composition according to claim 78, wherein said V, domain comprises the amino acid sequence of SEQ ID NO: 8.

### Claim 81 (depends on 78)

A method for treating at least one disease or condition selected from the group consisting of an autoimmune disease, inflammatory conditions, allergies, allergic conditions, hypersensitivity reactions, and organ or tissue transplant rejection in a subject in need thereof comprising administering to the subject an effective amount of the pharmaceutical composition according to claim 78.

### Claim 82 (depends on 81)

The method according to claim 81, wherein said disease is selected from psoriasis, systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, spondyloarthropathies, systemic sclerosis, idiopathic inflammatory myopathies, Sjogren's syndrome, systemic vasculitis, sarcoidosis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, thyroiditis, diabetes mellitus, immune-mediated renal disease, demyelinating diseases of the central and peripheral nervous systems multiple sclerosis, idiopathic demyelinating polyneuropathy or Guillain Barre syndrome, chronic inflammatory demyelinating polyneuropathy, hepatobiliary diseases, autoimmune chronic active hepatitis, primary biliary cirrhosis, granulomatous hepatitis, sclerosing cholangitis, inflammatory bowel disease, gluten-sensitive enteropathy, Whipple's disease, autoimmune or immune-mediated skin diseases, bullous skin diseases, erythema multiforme, contact dermatitis, allergic diseases, asthma, allergic rhinitis, atopic dermatitis, food hypersensitivity, urticaria, immunologic diseases of the lung, eosinophilic pneumonia, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, autoimmune haematological disorders, hemolytic anaemia, aplastic anaemia, pure red cell anaemia, idiopathic thrombocytopenia, autoimmune inflammatory bowel disease, ulcerative colitis, Crohn's disease, Irritable Bowel Syndrome, uveitis, transplantation associated diseases, graft rejection, and graft-versus-host-disease.