NZ782617B2

NZ782617B2 - Antibody molecules to APRIL and uses thereof

Info

Publication number: NZ782617B2
Application number: NZ782617A
Authority: NZ
Inventors: Hall Hedy Adari; Gregory Babcock; James R Myette; Boopathy Ramakrishnan; Zachary Holmes Shriver; Karthik Viswanathan; Andrew M Wollacott
Original assignee: Visterra Inc
Filing date: 2016-11-23
Publication date: 2025-09-30

Abstract

Antibody molecules that specifically bind to APRIL are disclosed. The antibody molecules can be used to treat, prevent, and/or diagnose disorders, such as IgA nephropathy.

Claims

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

1. An anti-A PRoliferation Inducing Ligand (APRIL) antibody comprising a heavy chain comprising a heavy chain mentarity determining region (VH CDR) 1, a VH CDR2, and a VH CDR3 5 and a light chain variable domain (VL), wherein the VL comprises the amino acid sequence of SEQ ID NO: 286, and wherein: a) the VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 11; b) the VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 12; and c) the VH CDR3 comprises the amino acid ce set forth in SEQ ID NO: 13, by the 10 Chothia numbering system.

2. The anti-APRIL antibody of claim 1 further comprising a constant region linked to the heavy chain variable region (VH) and or VL. 15

3. The PRIL antibody of claim 1 or claim 2, wherein the anti-APRIL antibody comprises: (a) a heavy chain constant region of IgG1, IgG2, IgG3, or IgG4; (b) a light chain constant region of kappa or lambda light chain; or (c) both (a) and (b). 20

4. The PRIL antibody of any one of claims 1–3, wherein the anti-APRIL antibody comprises a nt crystallizable (Fc) region, wherein the Fc region comprises one or more mutations located at the interface between the constant heavy chain (CH) 2 and CH3 domains.

5. A nucleic acid encoding the anti-APRIL dy of any one of claims 1–4.

6. A vector comprising the nucleic acid of claim 5.

7. An isolated cell comprising the vector of claim 6. 30

8. A method of producing an anti-APRIL antibody, the method comprising culturing the isolated cell of claim 7, thereby producing the anti-APRIL antibody.

9. The method of claim 8, further comprising ing or ing the anti-APRIL antibody.

10. A composition comprising the anti-APRIL antibody of any one of claims 1–4 and a pharmaceutically acceptable carrier.

11. A kit comprising the anti-APRIL antibody of any one of claims 1–4 or the composition of claim 5 10, and instructions to use the anti-APRIL antibody of any one of claims 1–4 or the composition of claim 10.

12. A container comprising the PRIL antibody of any one of claims 1–4 or the composition of claim 10.

13. An anti-APRIL dy conjugate, comprising the anti-APRIL antibody of any one of claims 1–4 conjugated to a substance.

14. The anti-APRIL antibody conjugate of claim 13, wherein the substance comprises a toxin, a moiety, 15 a therapeutic drug, a radiation- emitting compound, a molecule of plant, fungal or bacterial origin, a biological protein, a protein toxin, a particle, a recombinant viral particle, a radioactive isotope, or a combination thereof.

15. An anti-APRIL antibody derivative, comprising the anti-APRIL antibody of any one of claims 1-4 20 derivatized to a functional le or one or more molecular entities.

16. The anti-APRIL antibody derivative of claim 15, wherein the functional molecule or the one or more molecular es comprises a e, a protein, an antibody, a detectable agent, a toxin, a pharmaceutical agent, or a combination thereof.

17. Use of the anti-APRIL dy of any one of claims 1–4, the composition of claim 10, the anti- APRIL antibody conjugate of claim 13 or claim 14, or the anti-APRIL antibody derivative of claim 15 or 16 in the manufacture of a ment for a disease or condition in a subject, wherein the disease or ion comprises IgA nephropathy.

18. An in vitro or ex vivo method of detecting an APRIL molecule, the method comprising contacting a cell or a sample from a t with the anti-APRIL antibody of any one of claims 1–4 in vitro or ex vivo, thereby detecting the APRIL molecule. ECianeES EMouse Spreéiminary Emmuaizatian APREL Binding % Receptar iii) Sisetvm if? scheme (primw AA§§§§§A§5§9§g}Mmmw??ggié?g AAAAAAAAAAAAAAAAAAAA i boast} Human Mame Human EMouse APREL APREL APRii Exams: (i-i-E-Ew?n?) 32.0 §<10 501-863 - -- $014364 $343014: iagei 591377 38-09% Eagm 5014279 ' run—W 501-104 gsuaom igGl 014135 80:31-8 igGEb run—W : 8-00m g ...................................................................................... 3-0013 ' igGi ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Cicne ED Mause greiiminary immunizatian APREL Binding % Recepmr ii) isotype ED scheme {prime- {EUSA,A4SGB [Hacking f = 5 Most} Human Mame Human Mame 2”: a 1 ‘ E 1.57 0.49 “1'43 <10 2.38 0.7 94.2 <13 2 3‘. 7 £3.38 392.5 <10 l 4 0.21 92.8 g , {MMME‘V‘VHMM EigM §M~M~M~H~M«(w ; . 1 v :gM ’i~!‘v’§~é~in) 1.83 0.05 12.5 510 §:gM {Ps4»-M-M-H»-M§ . . . :gM {M-E‘v’iui‘v’E-ivi-M) 2.80 3.09 32.9 <10 i {MM-M-é-i-M) * ' i " Human APREL E 020“; .2 0 4 Log {Antibody} (mg/mi) Manse APREL ? 0220? 1 5 I ' a 1313 a 01—002 v a“: m 9 . a 1.0 ...................... “w ® 01—062 ............. A450 ...................." m 024 1 ‘E ......... A Amy-'5 -1 Log {Antibody} (mg/mi) HQ. 2% ................................................................................................................................................... ?nding Receptcr Biecking {approximate EC503 {appmximate 3ng) 53 ngfmi sag/min Human Meme Human §M0use APREL APRiL APREL EAPREL $14392 46,6 4.2 >1GGGG >190€3G 25.2 -- ............................ ............................. .............................,.......................................................... 314.8 38.3 ____________________________ _____________________________ _____________________________ ____________________________.L____________________________ 3: 39m 28 w $3069 315 w we >1Qeaa >1DGGO n 02—113-?05 932 $2530 Aprynm-729.5 M 15.1 Mg“ 3 1111111311101": L mediated NF k8 Activat?en 30000 G 1313 a A v 01—0

19. ~;~~-.~.~.~..... @ 014362 20001) ® A A (114181 ...... ............::::::::::: “““““ a 01n1 17 ? 02—1 11 A Amy—14 10001) 0.01 1 100 10000 EgG (nM) F113,. £1 APREL Binding a» 2218 A 2419 «9 2621 A456 Q 2922 E23 3125 m 3530 Q 1313 V 0201 10 1000 100000 mi» Apriiyu1~1 [Ab], ng/mL A 3525 Ab 5cm {nglm 1.1 5C5.) (111