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NZ782606B2 - Antibody molecules to APRIL and uses thereof - Google Patents
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NZ782606B2 - Antibody molecules to APRIL and uses thereof - Google Patents

Antibody molecules to APRIL and uses thereof

Info

Publication number
NZ782606B2
NZ782606B2 NZ782606A NZ78260616A NZ782606B2 NZ 782606 B2 NZ782606 B2 NZ 782606B2 NZ 782606 A NZ782606 A NZ 782606A NZ 78260616 A NZ78260616 A NZ 78260616A NZ 782606 B2 NZ782606 B2 NZ 782606B2
Authority
NZ
New Zealand
Prior art keywords
april
antibody
april antibody
aprel
human
Prior art date
Application number
NZ782606A
Other versions
NZ782606A (en
Inventor
Hall Hedy Adari
Gregory Babcock
James R Myette
Boopathy Ramakrishnan
Zachary Holmes Shriver
Karthik Viswanathan
Andrew M Wollacott
Original Assignee
Visterra Inc
Filing date
Publication date
Application filed by Visterra Inc filed Critical Visterra Inc
Publication of NZ782606A publication Critical patent/NZ782606A/en
Publication of NZ782606B2 publication Critical patent/NZ782606B2/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/54Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/545Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241Tumor Necrosis Factors
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2875Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/10Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14Specific host cells or culture conditions, e.g. components, pH or temperature
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94Stability, e.g. half-life, pH, temperature or enzyme-resistance

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 (19)

What is claimed is:
1. An anti-A PRoliferation Inducing Ligand (APRIL) dy sing a heavy chain variable domain (VH) and a light chain variable domain (VL) wherein: 5 a) the VH comprises the amino acid sequence of SEQ ID NO: 296; and b) the VL comprises the amino acid sequence of SEQ ID NO: 286.
2. The anti-APRIL antibody of claim 1 further comprising a constant region linked to the VH and or
3. The anti-APRIL 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).
4. The PRIL antibody of any one of claims 1–3, wherein the anti-APRIL antibody comprises a fragment crystallizable (Fc) region, wherein the Fc region ses one or more mutations located at the ace between the nt heavy chain (CH) 2 and CH3 domains. 20
5. A nucleic acid encoding the anti-APRIL antibody 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.
8. A method of producing an anti-APRIL antibody, the method comprising culturing the ed cell of claim 7, thereby producing the anti-APRIL antibody.
9. The method of claim 8, further comprising isolating or purifying 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 PRIL antibody of any one of claims 1–4 or the composition of claim 10, and instructions to use the anti-APRIL antibody of any one of claims 1–4 or the composition of claim 10. 5
12. A container sing the anti-APRIL antibody of any one of claims 1–4 or the composition of claim 10.
13. An anti-APRIL antibody 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, a therapeutic drug, a radiation- emitting nd, a molecule of plant, fungal or bacterial origin, a biological protein, a protein toxin, a particle, a recombinant viral particle, a radioactive e, or a combination f.
15. An anti-APRIL antibody derivative, comprising the anti-APRIL antibody of any one of claims 1– 4 tized to a functional molecule or one or more molecular entities.
16. The anti-APRIL antibody derivative of claim 15, wherein the functional molecule or the one or 20 more molecular entities comprises a peptide, a protein, an antibody, a detectable agent, a toxin, a pharmaceutical agent, or a combination thereof.
17. Use of the anti-APRIL antibody 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 25 15 or claim 16 in the manufacture of a medicament for treating a disease or condition in a t, 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 subject with the PRIL dy of any one of claims 1–4 in vitro or 30 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 AAAAAAAAAAAAAAAAAAAAAAAAAA i boast} Human Mame Human EMouse APREL APREL APRii Exams: (i-i-E-Ew?n?) 32.0 §<10 501-863 - -- $014364 4: 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 ng 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 {Mnt‘v’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 ody} (mg/mi) HQ. 2% ................................................................................................................................................... ?nding Receptcr Biecking {approximate EC503 {appmximate 3ng) (3066253 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": OfAPREL mediated NF k8 Activat?en 30000 G 1313 a A v 01—0
19. ~;~~-.~.~.~..... @ 014362 20001) ® A ...... ............::::::::::: “““““ 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
NZ782606A 2016-11-23 Antibody molecules to APRIL and uses thereof NZ782606B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201562259897P 2015-11-25 2015-11-25
US201662313684P 2016-03-25 2016-03-25
US201662399087P 2016-09-23 2016-09-23
US201662422848P 2016-11-16 2016-11-16
NZ742879A NZ742879B2 (en) 2016-11-23 Antibody molecules to april and uses thereof

Publications (2)

Publication Number Publication Date
NZ782606A NZ782606A (en) 2025-06-27
NZ782606B2 true NZ782606B2 (en) 2025-09-30

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