Anti-IL-17A Antibodies

• US 10,442,869 B2
• Filed: 09/01/2016
• Issued: 10/15/2019
• Est. Priority Date: 09/26/2014
• Status: Active Grant

• Current Assignee: Closed Joint-Stock Company "BIOCAD
• Original Assignee: Closed Joint-Stock Company "BIOCAD
• Inventors: Ulitin, Andrey Borisovich, Evdokimov, Stanislav Rudolfovich, Soloviev, Valeriy Vladimirovich, Chernyh, Yulia Sergeevna, Goncharova, Olga Vladimirovna, Korzhavin, Dmitriy Valerievich, Chernovskaya, Tatyana Veniaminovna, Nemankin, Timofey Aleksandrovich, Ivanov, Roman Alexeevich, Morozov, Dmitriy Valentinovich, Ekimova, Victoria Mikhailovna, Sofronova, Ekaterina Vladimirovna, Ustyugov, Yakov Yurevich
• Primary Examiner(s): Jiang, Dong
• Application Number:
  US15/254,225
• Publication Number:
  US 20170066843A1
• Time in Patent Office: 1,139 Days
• Field of Search: None
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/10 : for petit-mal
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 : for treating abuse or dependence
• CPC Class Codes: A61P 25/32 : Alcohol-abuse
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/08 : for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/06 : for tuberculosis
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/18 : of the parathyroid hormones
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/244 : Interleukins [IL]
• CPC Class Codes: C07K 16/461 : Igs containing Ig-regions, -domains or -residues form different species
• CPC Class Codes: C07K 2317/22 : from camelids, e.g. camel, llama or dromedary
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

The monoclonal IgG-type antibodies were suggested comprising variable domains represented by a combination of VHH-derivative with a variable domain of the light chain V_L. Said antibodies can comprise amino acid substitutions at positions 44 and 45 (Kabat numbering) or combinations thereof. Antibodies of the invention possess increased affinity and improved aggregation stability.

Claims

1. A monoclonal IgG antibody or fragment thereof that specifically binds to human IL-17A comprising a heavy chain variable domain V_HH, and a light chain variable domain V_L comprising the amino acid sequence of SEQ ID NO:

8, wherein the V_HH comprises;

a) HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO;

4, SEQ ID NO;

5 and SEQ ID NO;

6, respectively;

or

b) a variant of a), comprising one amino acid substitution selected from the group consisting of;

the amino acid at the 6^th position of SEQ ID. NO;

4 is N, K, R, E, W, M, Q, D, F, V, L or A;

the amino acid at the 7^th position of SEQ ID. NO;

4 is S;

the amino acid at the 8^th position of SEQ ID. NO;

4 is I;

the amino acid at the 9^th position of SEQ ID. NO;

4 is L, A, I, S, R, V, N, Q or M;

the amino acid at the 1^st position of SEQ ID NO;

5 is G or L;

the amino acid at the 4^th position of SEQ ID NO;

5 is A;

the amino acid at the 7^th position of SEQ ID NO;

5 is S, R, P, D, I, T, E, K, A, L or W;

the amino acid at the 3^rd position of SEQ ID NO;

6 is K, S, A, T, D or G;

the amino acid at the 4^th position of SEQ ID NO;

6 is K;

the amino acid at the 5^th position of SEQ ID NO;

6 is G, Y, H, D, W or K;

the amino acid at the 6^th position of SEQ ID NO;

6 is A, V, S, L M or H;

the amino acid at the 8^th position of SEQ ID NO;

6 is E, G, A, R, V, K or Q;

the amino acid at the 9^th position of SEQ ID NO;

6 is S or N;

the amino acid at the 10^th position of SEQ ID NO;

6 is G, S, P, V, R, N or K;

the amino acid at the 11^th position of SEQ ID NO;

6 is V, M, C, T, L, Y, A, H, G or I;

the amino acid at the 12^th position of SEQ ID NO;

6 is W or S;

the amino acid at the 13^th position of SEQ ID NO;

6 is R, V, L, A, W, K, G, Q or I;

the amino acid at the 14^th position of SEQ ID NO;

6 is L, A or S; and

the amino acid at the 15^th position of SEQ ID NO;

6 is T, L, P, N, A, Q, F, I or D.

2. The antibody or the fragment thereof according to claim 1,

wherein:

the HCDR1 comprises the amino acid sequence with the sequence identity of SEQ ID NO;

4;

the HCDR2 comprises the amino acid sequence with the sequence identity of SEQ ID NO;

5; and

the HCDR3 comprises the amino acid sequence with the sequence identity of SEQ ID NO;

6.

3. The antibody or the fragment thereof according to claim 2 wherein the V_HH comprises an amino acid sequence that is at least 90% identical to SEQ ID NO:

7.

4. The antibody or the fragment thereof according to claim 3, wherein said V_HH comprises an amino acid sequence of SEQ ID NO:

7.

5. The antibody according to claim 1, wherein said antibody is IgG1, IgG2, IgG3 or IgG4.

6. The antibody according to claim 5, comprising a Fc region as a part of IgG.

7. A pharmaceutical composition comprising the antibody or the fragment thereof according to claim 1, and one or more pharmaceutically suitable excipient, diluent or carrier.

8. The pharmaceutical composition according to claim 7, further comprising an active pharmaceutical ingredient which is a TNF-α

inhibitor.

9. A monoclonal IgG antibody or fragment thereof that specifically binds to human IL-17A comprising a heavy chain variable domain VHH comprising HCDR1, HCDR2 and HCDR3, and a light chain variable domain VL comprising the amino acid sequence of SEQ ID NO:

8, wherein the HCDR1, the HCDR2 and the HCDR3 of the VHH comprise the amino acid sequences of SEQ ID NO;

4, SEQ ID NO;

5 and SEQ ID NO;

6, respectively.