Anti-Orai1 antibody

• US 10,851,162 B2
• Filed: 07/02/2019
• Issued: 12/01/2020
• Est. Priority Date: 08/07/2014
• Status: Active Grant

• Current Assignee: Daiichi Sankyo Company Limited
• Original Assignee: Daiichi Sankyo Company Limited
• Inventors: Komai, Tomoaki, Kimura, Takako, Baba, Daichi, Onodera, Yoshikuni, Tanaka, Kento, Kagari, Takashi, Aki, Anri, Nagaoka, Nobumi
• Primary Examiner(s): Li, Ruixiang
• Application Number:
  US16/460,632
• Publication Number:
  US 20190322740A1
• Time in Patent Office: 518 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• 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 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 13/12 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 17/00 Drugs for dermatological disorders
• 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 21/00 Drugs for disorders of the muscular or neuromuscular system
• 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 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 27/16 Otologicals
• 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 3/10 : for hyperglycaemia, e.g. antidiabetics
• 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 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 7/06 : Antianaemics
• 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 16/18 : against material from animals or humans
• CPC Class Codes: C07K 16/28 : against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/46 : Hybrid immunoglobulins hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/51 : Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 : Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/524 : CH2 domain
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• 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 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/71 : Decreased effector function due to an Fc-modification
• 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
• CPC Class Codes: C12N 15/09 : Recombinant DNA-technology
• CPC Class Codes: C12N 5/10 : Cells modified by introduction of foreign genetic material

Abstract

It is intended to provide a therapeutic and/or prophylactic agent for transplant rejections, immunological diseases, allergic diseases, inflammatory diseases, thrombosis, cancers, etc., targeting human Orai1. The present invention provides, for example, a pharmaceutical composition comprising an antibody that specifically recognizes human Orai1 and has the activity of inhibiting human T cell activation.

Claims

1. An antibody or an antigen binding fragment of the antibody which specifically binds to the amino acid sequence represented by SEQ ID NO:

2, wherein the heavy chain sequence comprises a variable region having CDRH1, CDRH2, and CDRH3, and

the light chain sequence comprises a variable region having CDRL1, CDRL2, and CDRL3 wherein the antibody or antigen binding fragment of the antibody is characterized by one of the following;

(a) wherein the CDRH1 consists of the amino acid sequence represented by SEQ ID NO;

102, the CDRH2 consists of the amino acid sequence represented by SEQ ID NO;

106, the CDRH3 consists of the amino acid sequence represented by SEQ ID NO;

110, the CDRL1 consists of the amino acid sequence represented by SEQ ID NO;

94, the CDRL2 consists of the amino acid sequence represented by SEQ ID NO;

97, and the CDRL3 consists of the amino acid sequence represented by SEQ ID NO;

101;

(b) wherein the CDRH1 consists of the amino acid sequence represented by SEQ ID NO;

102, the CDRH2 consists of the amino acid sequence represented by SEQ ID NO;

106, the CDRH3 consists of the amino acid sequence represented by SEQ ID NO;

110, the CDRL1 consists of the amino acid sequence represented by SEQ ID NO;

95, the CDRL2 consists of the amino acid sequence represented by SEQ ID NO;

98, and the CDRL3 consists of the amino acid sequence represented by SEQ ID NO;

101;

(c) wherein the CDRH1 consists of the amino acid sequence represented by SEQ ID NO;

102, the CDRH2 consists of the amino acid sequence represented by SEQ ID NO;

107, the CDRH3 consists of the amino acid sequence represented by SEQ ID NO;

110, the CDRL1 consists of the amino acid sequence represented by SEQ ID NO;

93, the CDRL2 consists of the amino acid sequence represented by SEQ ID NO;

96, and the CDRL3 consists of the amino acid sequence represented by SEQ ID NO;

101;

(d) wherein the CDRH1 consists of the amino acid sequence represented by SEQ ID NO;

102, the CDRH2 consists of the amino acid sequence represented by SEQ ID NO;

108, the CDRH3 consists of the amino acid sequence represented by SEQ ID NO;

110, the CDRL1 consists of the amino acid sequence represented by SEQ ID NO;

93, the CDRL2 consists of the amino acid sequence represented by SEQ ID NO;

96, and the CDRL3 consists of the amino acid sequence represented by SEQ ID NO;

101; and

(e) wherein the CDRH1 consists of the amino acid sequence represented by SEQ ID NO;

102, the CDRH2 consists of the amino acid sequence represented by SEQ ID NO;

104, the CDRH3 consists of the amino acid sequence represented by SEQ ID NO;

109, the CDRL1 consists of the amino acid sequence represented by SEQ ID NO;

93, the CDRL2 consists of the amino acid sequence represented by SEQ ID NO;

96, and the CDRL3 consists of the amino acid sequence represented by SEQ ID NO;

101.

2. The antibody or the antigen binding fragment of the antibody according to claim 1, wherein the heavy chain sequence comprises a variable region having CDRH1, CDRH2, and CDRH3, wherein the CDRH1 consists of the amino acid sequence represented by SEQ ID NO:

102, the CDRH2 consists of the amino acid sequence represented by SEQ ID NO;

106, and the CDRH3 consists of the amino acid sequence represented by SEQ ID NO;

110; and

the light chain sequence comprises a variable region having CDRL1, CDRL2, and CDRL3, wherein the CDRL1 consists of the amino acid sequence represented by SEQ ID NO;

94, the CDRL2 consists of the amino acid sequence represented by SEQ ID NO;

97, and the CDRL3 consists of the amino acid sequence represented by SEQ ID NO;

101.

3. The antibody or the antigen binding fragment of the antibody according to claim 1, wherein the heavy chain sequence comprises a variable region having CDRH1, CDRH2, and CDRH3, wherein the CDRH1 consists of the amino acid sequence represented by SEQ ID NO:

102, the CDRH2 consists of the amino acid sequence represented by SEQ ID NO;

106, and the CDRH3 consists of the amino acid sequence represented by SEQ ID NO;

110; and

the light chain sequence comprises a variable region having CDRL1, CDRL2, and CDRL3, wherein the CDRL1 consists of the amino acid sequence represented by SEQ ID NO;

95, the CDRL2 consists of the amino acid sequence represented by SEQ ID NO;

98, and the CDRL3 consists of the amino acid sequence represented by SEQ ID NO;

101.

4. The antibody or the antigen binding fragment of the antibody according to claim 1, wherein the heavy chain sequence comprises a variable region having CDRH1, CDRH2, and CDRH3, wherein the CDRH1 consists of the amino acid sequence represented by SEQ ID NO:

102, the CDRH2 consists of the amino acid sequence represented by SEQ ID NO;

107, and the CDRH3 consists of the amino acid sequence represented by SEQ ID NO;

110; and

the light chain sequence comprises a variable region having CDRL1, CDRL2, and CDRL3, wherein the CDRL1 consists of the amino acid sequence represented by SEQ ID NO;

93, the CDRL2 consists of the amino acid sequence represented by SEQ ID NO;

96, and the CDRL3 consists of the amino acid sequence represented by SEQ ID NO;

101.

5. The antibody or the antigen binding fragment of the antibody according to claim 1, wherein the heavy chain sequence comprises a variable region having CDRH1, CDRH2, and CDRH3, wherein the CDRH1 consists of the amino acid sequence represented by SEQ ID NO:

102, the CDRH2 consists of the amino acid sequence represented by SEQ ID NO;

108, and the CDRH3 consists of the amino acid sequence represented by SEQ ID NO;

110; and

the light chain sequence comprises a variable region having CDRL1, CDRL2, and CDRL3, wherein the CDRL1 consists of the amino acid sequence represented by SEQ ID NO;

93, the CDRL2 consists of the amino acid sequence represented by SEQ ID NO;

96, and the CDRL3 consists of the amino acid sequence represented by SEQ ID NO;

101.

6. The antibody or the antigen binding fragment of the antibody according to claim 1, wherein the heavy chain sequence comprises a variable region having CDRH1, CDRH2, and CDRH3, wherein the CDRH1 consists of the amino acid sequence represented by SEQ ID NO:

102, the CDRH2 consists of the amino acid sequence represented by SEQ ID NO;

104, and the CDRH3 consists of the amino acid sequence represented by SEQ ID NO;

109; and

the light chain sequence comprises a variable region having CDRL1, CDRL2, and CDRL3, wherein the CDRL1 consists of the amino acid sequence represented by SEQ ID NO;

93, the CDRL2 consists of the amino acid sequence represented by SEQ ID NO;

96, and the CDRL3 consists of the amino acid sequence represented by SEQ ID NO;

101.

7. The antibody or the antigen binding fragment of the antibody according to claim 1, wherein the antibody comprises a heavy chain variable region sequence consisting of amino acid residues from positions 20 to 136 in the amino acid sequence represented by SEQ ID NO:

62 and a light chain variable region sequence consisting of amino acid residues from positions 21 to 126 in the amino acid sequence represented by SEQ ID NO;

58.

8. The antibody or the antigen binding fragment of the antibody according to claim 7, wherein the antibody consists of a heavy chain sequence consisting of amino acid residues from positions 20 to 465 or 20 to 466 in the amino acid sequence represented by SEQ ID NO:

62 and a light chain sequence consisting of amino acid residues from positions 21 to 234 in the amino acid sequence represented by SEQ ID NO;

58.

9. The antibody or the antigen binding fragment of the antibody according to claim 1, wherein the antibody comprises a heavy chain variable region sequence consisting of amino acid residues from positions 20 to 136 in the amino acid sequence represented by SEQ ID NO:

62 and a light chain variable region sequence consisting of amino acid residues from positions 21 to 126 in the amino acid sequence represented by SEQ ID NO;

60.

10. The antibody or the antigen binding fragment of the antibody according to claim 9, wherein the antibody consists of a heavy chain sequence consisting of amino acid residues from positions 20 to 465 or 20 to 466 in the amino acid sequence represented by SEQ ID NO:

62 and a light chain sequence consisting of amino acid residues from positions 21 to 234 in the amino acid sequence represented by SEQ ID NO;

60.

11. The antibody or the antigen binding fragment of the antibody according to claim 1, wherein the antibody comprises a heavy chain variable region sequence consisting of amino acid residues from positions 20 to 136 in the amino acid sequence represented by SEQ ID NO:

64 and a light chain variable region sequence consisting of amino acid residues from positions 21 to 126 in the amino acid sequence represented by SEQ ID NO;

56.

12. The antibody or the antigen binding fragment of the antibody according to claim 11, wherein the antibody consists of a heavy chain sequence consisting of amino acid residues from positions 20 to 465 or 20 to 466 in the amino acid sequence represented by SEQ ID NO:

64 and a light chain sequence consisting of amino acid residues from positions 21 to 234 in the amino acid sequence represented by SEQ ID NO;

56.

13. The antibody or the antigen binding fragment of the antibody according to claim 1, wherein the antibody comprises a heavy chain variable region sequence consisting of amino acid residues from positions 20 to 136 in the amino acid sequence represented by SEQ ID NO:

66 and a light chain variable region sequence consisting of amino acid residues from positions 21 to 126 in the amino acid sequence represented by SEQ ID NO;

56.

14. The antibody or the antigen binding fragment of the antibody according to claim 13, wherein the antibody consists of a heavy chain sequence consisting of amino acid residues from positions 20 to 465 or 20 to 466 in the amino acid sequence represented by SEQ ID NO:

66 and a light chain sequence consisting of amino acid residues from positions 21 to 234 in the amino acid sequence represented by SEQ ID NO;

56.

15. The antibody or the antigen binding fragment of the antibody according to claim 1, wherein the antibody comprises a heavy chain variable region sequence consisting of amino acid residues from positions 20 to 136 in the amino acid sequence represented by SEQ ID NO:

43 and a light chain variable region sequence consisting of amino acid residues from positions 21 to 126 in the amino acid sequence represented by SEQ ID NO;

56.

16. The antibody or the antigen binding fragment of the antibody according to claim 15, wherein the antibody consists of a heavy chain sequence consisting of amino acid residues from positions 20 to 465 or 20 to 466 in the amino acid sequence represented by SEQ ID NO:

43 and a light chain sequence consisting of amino acid residues from positions 21 to 235 in the amino acid sequence represented by SEQ ID NO;

56.

17. The antigen binding fragment of the antibody according to claim 1, wherein the antigen binding fragment is selected from the group consisting of Fab, F(ab′

)2, Fab′

, and Fv.

18. The antibody according to claim 1, wherein the antibody is an scFv.

19. A pharmaceutical composition comprising at least any one antibody or antigen binding fragment of the antibody according to claim 1.