ANTIBODIES TO IL-15

• US 20190315853A1
• Filed: 05/24/2019
• Published: 10/17/2019
• Est. Priority Date: 07/02/2014
• Status: Active Grant

• Current Assignee: Calypso Biotech SA (Calypso Biotech BV)
• Original Assignee: Calypso Biotech SA (Calypso Biotech BV)
• Inventors: VICARI, ALAIN, LEGER, OLIVIER
• Granted Patent: US 11,130,806 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• 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: G01N 2333/5443 : IL-15
• CPC Class Codes: G01N 2333/7155 : for interleukins [IL]
• CPC Class Codes: G01N 33/6869 : Interleukin
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to antibodies binding IL-15, in particular humanized antibodies. In particular, the anti-IL-15 antibodies according to the invention are able to neutralize IL-15 activity and are useful in the prevention and/or treatment of an autoimmune disease and/or inflammatory disorder, a malignancy, transplant rejection, metabolic condition and/or an infectious disease caused by parasitic, viral or bacterial pathogens.

Claims

1. A method of preventing and/or treating an IL-15 related disease or disorder comprising administering in a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof comprising:

(1) a heavy chain variable region of SEQ ID NO;

5 or any variant thereof wherein 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acids of said sequence are substituted by a different amino acid, and

(2) a light chain variable region of SEQ ID NO;

24 or any variant thereof wherein 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids of said sequence are substituted by a different amino acid,

or an antigen-binding fragment thereof;

or a pharmaceutical composition thereof.

2. The method according to claim 1, wherein the IL-15 related disease or disorder is selected from an autoimmune disease, an inflammatory disorder, a malignancy, a metabolic condition, an infectious disease caused by parasitic, viral or bacterial pathogens, amyloid related disorders and/or a transplant rejection.

3. The method according to claim 1, wherein the IL-15 related disease or disorder is an autoimmune disorder.

4. The method according to claim 1, wherein the IL-15 related disease or disorder is eosinophilic esophagitis.

5. The method according to claim 1, wherein the IL-15 related disease or disorder is selected from rheumatoid arthritis, psoriasis, celiac disease, refractory celiac disease, sarcoidosis, inflammatory bowel disease, hepatitis C-induced liver diseases, multiple sclerosis, auto-immune hepatitis, primary biliary cirrhosis, sclerosing cholangitis, biliary atresia, alopecia areata, transplant rejection, inflammatory diseases of the central nervous system, Alzheimer'"'"'s disease, viral infections, and Hantaan viral infections and eosinophilic esophagitis.

6. The method according to claim 1, wherein the IL-15 related disease or disorder is celiac disease.

7. The method according to claim 1, wherein the IL-15 related disease or disorder is alopecia areata.

8. The method according to claim 1, wherein said antibody or antigen-binding fragment thereof is to be administered in combination with a co-agent useful in the prevention and/or treatment of an autoimmune disease and/or inflammatory disorder, a malignancy, transplant rejection, metabolic condition and/or an infectious disease caused by parasitic, viral or bacterial pathogens, or a compound lowering intestinal inflammation, and/or protecting intestinal mucosa, and/or lowering the immune reactivity of gluten peptides, and/or modifying the gut microbiota.

9. The method according to claim 1, wherein the antibody or antigen-binding fragment thereof, comprises:

(1) a heavy chain variable region of SEQ ID NO;

5 or any variant thereof having at least 95% identity with SEQ ID NO;

5, and

(2) a light chain variable region of SEQ ID NO;

24 or any variant thereof having at least 95% identity with SEQ ID NO;

24,

or an antigen-binding fragment thereof.

10. The method according to claim 1, wherein the antibody is a humanized antibody.

11. The method according to claim 1, wherein the said antibody or antigen-binding fragment comprises:

(1) a heavy chain variable region of SEQ ID NO;

5 or any variant thereof wherein 1, 2, 3, 4, 5 or 6 amino acids selected among;

(i) arginine (R) at position H3 (VH RH3), methionine (M) at position H5 (VH MH5), alanine (A) at position H6 (VH AH6), alanine (A) at position H49 (VH AH49), within the heavy chain variable framework region, and/or

(ii) aspartic acid (D) at position H61 (VH DH61), serine (S) at position H62 (VH SH62), within the heavy chain CDR2, and/or

(iii) methionine (M) at position H98 (VH MH98), tryptophan (W) at position H100C (VH WH100C), methionine (M) at position H100E (VH MI-1100E), within the heavy chain CDR3,

are substituted by a different amino acid, and

(2) a light chain variable region of SEQ ID NO;

24 or any variant thereof wherein 1, 2, 3, or 4 amino acids selected among;

(i) tyrosine (Y) at position L36 (VL YL36), leucine (L) at position L46 (VL LL46), within the light chain variable framework region, and/or

(ii) aspartic acid (D) at position L91 (VL DL91), serine (S) at position L92 (VL SL92), within the light chain CDR3,

are substituted by a different amino acid.

12. The method according to claim 1, wherein the said antibody or antigen-binding fragment thereof comprises:

(1) said variant of SEQ ID NO;

5 has the amino acid sequence of SEQ ID NO;

5 except that;

(i) VH RH3 is substituted by glutamine (Q), and/or VH MH5 is substituted by valine (V), and/or VH AH6 is substituted by glutamic acid (E), and/or VH AH49 is substituted by serine (S), and/or

(ii) VH DH61 is substituted by glutamic acid (E), and/or VH SH62 is substituted by threonine (T), and/or

(iii) VH MH98 is substituted by leucine (L), phenylalanine (F), isoleucine (I), or alanine (A), and/or VH WH100C is substituted by tyrosine (Y), phenylalanine (F), or alanine (A), and/or VH MI-1100E is substituted by leucine (L), phenylalanine (F), or isoleucine (I), and/or

(2) said variant of SEQ ID NO;

24 has the amino acid sequence of SEQ ID NO;

24 except that;

(i) VL YL36 is substituted by phenylalanine (F), and/or VL LL46 is substituted by arginine (R), and/or

(ii) VL DL91 is substituted by glutamic acid (E), and/or VL SL92 is substituted by threonine (T).

13. The method according to claim 1, wherein the said antibody or antigen-binding fragment thereof comprises:

(1) a heavy chain variable region of amino acid sequence of SEQ ID NO;

5 except that;

(i) VH RH3 is substituted by glutamine (Q), and/or VH MH5 is substituted by valine (V), and/or VH AH6 is substituted by glutamic acid (E), and/or

(ii) VH SH62 is substituted by threonine (T), and/or

(iii) VH WH100C is substituted by tyrosine (Y), and

(2) a light chain variable region of amino acid sequence of SEQ ID NO;

24.

14. The method according to claim 1, wherein the said antibody or antigen-binding fragment thereof comprises:

(1) a heavy chain variable region selected from;

SEQ ID NO;

6, SEQ ID NO;

12, SEQ ID NO;

21, and SEQ ID NO;

5, and

(2) a light chain variable region of SEQ ID NO;

24.

15. The method according to claim 1, wherein the said antibody or antigen-binding fragment thereof comprises a heavy chain variable region of SEQ ID NO:

6 and a light chain variable region of SEQ ID NO;

24.