NZ779309B2 - Combination of il-4/il-13 pathway inhibitors and plasma cell ablation for treating allergy - Google Patents

Combination of il-4/il-13 pathway inhibitors and plasma cell ablation for treating allergy

Info

Publication number
NZ779309B2
NZ779309B2 NZ779309A NZ77930920A NZ779309B2 NZ 779309 B2 NZ779309 B2 NZ 779309B2 NZ 779309 A NZ779309 A NZ 779309A NZ 77930920 A NZ77930920 A NZ 77930920A NZ 779309 B2 NZ779309 B2 NZ 779309B2
Authority
NZ
New Zealand
Prior art keywords
seq
amino acid
acid sequence
antigen
binding domain
Prior art date
Application number
NZ779309A
Other versions
NZ779309A (en
Inventor
Seblewongel Asrat
Andre Limnander
Andrew J Murphy
Jamie Orengo
George D Yancopoulos
Original Assignee
Regeneron Pharmaceuticals Inc
Filing date
Publication date
Application filed by Regeneron Pharmaceuticals Inc filed Critical Regeneron Pharmaceuticals Inc
Priority claimed from PCT/US2020/023988 external-priority patent/WO2020191346A1/en
Publication of NZ779309A publication Critical patent/NZ779309A/en
Publication of NZ779309B2 publication Critical patent/NZ779309B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • A61K2039/543—Mucosal route intranasal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2809—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878—Immunoglobulins [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-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present disclosure provides methods for treating allergy comprising selecting a patient with an allergy and administering a therapeutically effective amount of an IL-4/IL-13 pathway inhibitor (e.g ., an anti-IL-4 receptor antibody or antigen-binding fragment thereof) in combination with a therapeutically effective amount of an agent that depletes plasma cells (e.g ., an anti-BCMA/anti-CD3 bispecific antibody). In certain embodiments, a plasma cell ablating agent such as an anti-BCMA/anti-CD3 bispecific antibody ablates the plasma cells, including IgE+ plasma cells, while the IL-4/IL-13 pathway inhibitor prevents the generation of new IgE+ plasma cells, thus eliminating allergen-specific IgE in the patient.

Claims (30)

CLAIMS :
1. Use of an IL-4/IL-13 pathway inhibitor and a plasma cell ablating agent in the manufacture of a medicament for reducing or eliminating allergen-specific serum IgE in a subject in need thereof, wherein said subject has an allergic disease or disorder, a mast cell activation disorder or mastocytosis; and wherein the plasma cell ablating agent is an anti- BCMA/anti-CD3 bispecific antibody or antigen-binding fragment thereof comprising (i) a first antigen-binding domain that specifically binds to BCMA; and (ii) a second antigen- binding domain that specifically binds CD3.
2. Use of an IL-4/IL-13 pathway inhibitor and a plasma cell ablating agent in the manufacture of a medicament for treating allergy or reducing the severity of an allergic reaction to an allergen in a subject in need thereof, wherein said subject has an allergic disease or disorder, a mast cell activation disorder or mastocytosis; and wherein the plasma cell ablating agent is an anti-BCMA/anti-CD3 bispecific antibody or antigen-binding fragment thereof comprising (i) a first antigen-binding domain that specifically binds to BCMA; and (ii) a second antigen-binding domain that specifically binds CD3.
3. Use of a plasma cell ablating agent for treating allergy or reducing the severity of an allergic reaction to an allergen in a subject in need thereof, wherein said subject has an allergic disease or disorder, a mast cell activation disorder or mastocytosis, and wherein the subject is on a background therapy regimen comprising one or more doses of an IL-4/IL-13 pathway inhibitor; wherein the plasma cell ablating agent is an anti-BCMA/anti-CD3 bispecific antibody or antigen-binding fragment thereof comprising (i) a first antigen-binding domain that specifically binds to BCMA; and (ii) a second antigen-binding domain that specifically binds CD3.
4. Use of an IL-4/IL-13 pathway inhibitor in the manufacture of a medicament for reducing or eliminating allergen-specific serum IgE in a subject in need thereof, wherein said subject has an allergic disease or disorder, a mast cell activation disorder or mastocytosis; wherein the IL-4/IL-13 pathway inhibitor is to be administered in combination with a plasma cell ablating agent; and wherein the plasma cell ablating agent is an anti- BCMA/anti-CD3 bispecific antibody or antigen-binding fragment thereof comprising (i) a first antigen-binding domain that specifically binds to BCMA; and (ii) a second antigen- binding domain that specifically binds CD3.
5. Use of an IL-4/IL-13 pathway inhibitor in the manufacture of a medicament for treating allergy or reducing the severity of an allergic reaction to an allergen in a subject in need thereof, wherein said subject has an allergic disease or disorder, a mast cell activation disorder or mastocytosis; wherein the IL-4/IL-13 pathway inhibitor is to be administered in combination with a plasma cell ablating agent; and wherein the plasma cell ablating agent is an anti-BCMA/anti-CD3 bispecific antibody or antigen-binding fragment thereof comprising (i) a first antigen-binding domain that specifically binds to BCMA; and (ii) a second antigen- binding domain that specifically binds CD3.
6. Use of a plasma cell ablating agent in the manufacture of a medicament for reducing or eliminating allergen-specific serum IgE in a subject in need thereof, wherein said subject has an allergic disease or disorder, a mast cell activation disorder or mastocytosis; wherein the plasma cell ablating agent is to be administered in combination with a IL-4/IL-13 pathway inhibitor; and wherein the plasma cell ablating agent is an anti-BCMA/anti-CD3 bispecific antibody or antigen-binding fragment thereof comprising (i) a first antigen-binding domain that specifically binds to BCMA; and (ii) a second antigen-binding domain that specifically binds CD3.
7. Use of a plasma cell ablating agent in the manufacture of a medicament for treating allergy or reducing the severity of an allergic reaction to an allergen in a subject in need thereof, wherein said subject has an allergic disease or disorder, a mast cell activation disorder or mastocytosis; wherein the plasma cell ablating agent is to be administered in combination with a IL-4/IL-13 pathway inhibitor; and wherein the plasma cell ablating agent is an anti-BCMA/anti-CD3 bispecific antibody or antigen-binding fragment thereof comprising (i) a first antigen-binding domain that specifically binds to BCMA; and (ii) a second antigen-binding domain that specifically binds CD3.
8. The use of any one of claims 1-7, wherein the allergic disease or disorder is selected from the group consisting of allergic asthma, hay fever, chronic urticaria, food allergy, pollen allergy, and allergy due to an environmental (non-food) allergen.
9. The use of any one of claims 1-8, wherein the subject: - is at a risk of anaphylaxis due to an allergen, - has a seasonal allergy, - has a severe allergy, and/or - has an allergy due to one or more allergens selected from the group consisting of milk, a dairy product, egg, celery, sesame, wheat, meat, soy, fish, a fruit, shellfish, a sugar, peanut, a legume, a tree nut, dust, dust mite, pollen, insect venom, mold, animal fur, animal dander, wool, latex, a metal, a household cleaner, a detergent, medication, cosmetics, perfumes, a drug, therapeutic monoclonal antibodies, ragweed, grass and birch.
10. The use of any one of claims 1-9, wherein the IL-4/IL-13 pathway inhibitor is selected from the group consisting of an anti-IL-4 antibody, an anti-IL-13 antibody, an anti- IL-4/IL-13 bispecific antibody, an IL-4 receptor (IL-4R) inhibitor, an IL-4 trap, an IL-13 trap, and an anti-IL-4R antibody.
11. The use of claim 10, wherein the IL-4/IL-13 pathway inhibitor is an anti-IL- 4R antibody.
12. The use of claim 11, wherein the anti-IL-4R antibody comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) and three light chain CDRs (LCDR1, LCDR2 and LCDR3), wherein HCDR1 has the amino acid sequence of SEQ ID NO: 3, HCDR2 has the amino acid sequence of SEQ ID NO: 4, HCDR3 has the amino acid sequence of SEQ ID NO: 5, LCDR1 has the amino acid sequence of SEQ ID NO: 6, LCDR2 has the amino acid sequence of SEQ ID NO: 7, and LCDR3 has the amino acid sequence of SEQ ID NO: 8.
13. The use of claim 12, wherein the anti-IL-4R antibody comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.
14. The use of claim 11, wherein the anti-IL-4R antibody comprises a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence of SEQ ID NO: 9.
15. The use of claim 11, wherein the anti-IL-4R antibody comprises a heavy chain and a light chain, wherein the light chain has the amino acid sequence of SEQ ID NO: 10.
16. The use of claim 11, wherein the anti-IL-4R antibody comprises a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence of SEQ ID NO: 9 and the light chain has the amino acid sequence of SEQ ID NO: 10.
17. The use of claim 10, wherein the IL-4/IL-13 pathway inhibitor is dupilumab or a bioequivalent thereof.
18. The use of claim 10, wherein the IL-4/IL-13 pathway inhibitor is selected from the group consisting of dupilumab, pascolizumab, AMG317, MEDI2045, MEDI9314, tralokinumab, lebrikzimab, anrukinzumab, dectrekumab, GSK679586, MEDI7836, romilkimab, an IL-4 trap, an IL-13 trap, AER-003, and pitrakinra.
19. The use of any one of claims 1-18, wherein the first antigen-binding domain that specifically binds to BCMA comprises three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 12, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 20.
20. The use of claim 19, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 14, HCDR2 has the amino acid sequence of SEQ ID NO: 16, HCDR3 has the amino acid sequence of SEQ ID NO: 18, LCDR1 has the amino acid sequence of SEQ ID NO: 22, LCDR2 has the amino acid sequence of SEQ ID NO: 24, and LCDR3 has the amino acid sequence of SEQ ID NO: 26.
21. The use of any one of claims 1-20, wherein the second antigen-binding domain that specifically binds to CD3 comprises three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 28 and 36, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 20.
22. The use of claim 21, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 30 or 38, HCDR2 has the amino acid sequence of SEQ ID NO: 32 or 40, HCDR3 has the amino acid sequence of SEQ ID NO: 34 or 42, LCDR1 has the amino acid sequence of SEQ ID NO: 22, LCDR2 has the amino acid sequence of SEQ ID NO: 24, and LCDR3 has the amino acid sequence of SEQ ID NO: 26.
23. The use of any one of claims 1-18, wherein the anti-BCMA/anti-CD3 bispecific antibody or antigen-binding fragment thereof comprises: (a) a first antigen-binding domain that comprises HCDR1, HCDR2, and HCDR3 domains, respectively, comprising the amino acid sequences of SEQ ID NOs: 14, 16, and 18, and LCDR1, LCDR2, and LCDR3 domains, respectively, comprising the amino acid sequences of SEQ ID NOs: 22, 24, and 26; and (b) a second antigen-binding domain that comprises HCDR1, HCDR2, and HCDR3 domains, respectively, comprising the amino acid sequences of SEQ ID NOs: 30, 32, and 34, and LCDR1, LCDR2, and LCDR3 domains, respectively, comprising the amino acid sequences of SEQ ID NOs: 22, 24, and 26.
24. The use of any one of claims 1-18, wherein the anti-BCMA/anti-CD3 bispecific antibody or antigen-binding fragment thereof comprises: (a) a first antigen-binding domain that comprises HCDR1, HCDR2, and HCDR3 domains, respectively, comprising the amino acid sequences of SEQ ID NOs: 14, 16, and 18, and LCDR1, LCDR2, and LCDR3 domains, respectively, comprising the amino acid sequences of SEQ ID NOs: 22, 24, and 26; and (b) a second antigen-binding domain that comprises HCDR1, HCDR2, and HCDR3 domains, respectively, comprising the amino acid sequences of SEQ ID NOs: 38, 40, and 42, and LCDR1, LCDR2, and LCDR3 domains, respectively, comprising the amino acid sequences of SEQ ID NOs: 22, 24, and 26.
25. The use of claim 6, wherein: the IL-4/IL-13 pathway inhibitor is an anti-IL-4R antibody, wherein the anti-IL-4R antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:1 and an LCVR comprising the amino acid sequence of SEQ ID NO:2; and the anti-BCMA/anti-CD3 bispecific antibody or antigen-binding fragment thereof comprises (a) a first antigen-binding domain that comprises an HCVR comprising the amino acid sequence of SEQ ID NO:12 and an LCVR comprising the amino acid sequence of SEQ ID NO:20; and a second antigen-binding domain that comprises an HCVR comprising the amino acid sequence of SEQ ID NO:36 and an LCVR comprising the amino acid sequence of SEQ ID NO:20.
26. The use of any one of claims 1-25, wherein the IL-4/IL-13 pathway inhibitor is to be administered prior to the plasma cell ablating agent.
27. The use of any one of claims 1-25, wherein the IL-4/IL-13 pathway inhibitor is to be administered after the plasma cell ablating agent.
28. The use of any one of claims 1-25, wherein the IL-4/IL-13 pathway inhibitor and the plasma cell ablating agent are to be administered concurrently.
29. The use of any one of claims 1-28, wherein the medicament is to be administered with at least one additional therapeutic agent or therapy.
30. The use of claim 29, wherein the additional therapeutic agent is selected from the group consisting of an IgE antagonist, an anti-histamine, an anti-inflammatory agent, a corticosteroid, a leukotriene antagonist, a mast cell inhibitor, a bronchial dilator, a decongestant, epinephrine, an IL-1 antagonist, an IL-5 antagonist, an IL-31 antagonist, an IL- 33 antagonist, an IL-25 antagonist, interferon ?, a TNF antagonist, and a TSLP antagonist.
NZ779309A 2020-03-20 Combination of il-4/il-13 pathway inhibitors and plasma cell ablation for treating allergy NZ779309B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201962822022P 2019-03-21 2019-03-21
US202062957550P 2020-01-06 2020-01-06
PCT/US2020/023988 WO2020191346A1 (en) 2019-03-21 2020-03-20 Combination of il-4/il-13 pathway inhibitors and plasma cell ablation for treating allergy

Publications (2)

Publication Number Publication Date
NZ779309A NZ779309A (en) 2025-08-29
NZ779309B2 true NZ779309B2 (en) 2025-12-02

Family

ID=

Similar Documents

Publication Publication Date Title
CN113597328B (en) Combination of an IL-4/IL-13 pathway inhibitor and plasma cell ablation for the treatment of allergies
KR102645242B1 (en) Methods of treating inflammatory diseases
JPWO2020191346A5 (en)
JP2019531273A5 (en)
KR102679182B1 (en) Methods for treating or preventing asthma by administering an il-4r antagonist
CN105392497B (en) Methods of treating eosinophilic esophagitis with IL-4R inhibitors
JP2015523962A5 (en)
JP2016521713A5 (en)
JP2022169718A5 (en)
JP2025038193A5 (en)
RU2015156628A (en) METHODS FOR TREATING ALLERGIES AND INCREASING EFFECTIVENESS OF ALLERGEN-SPECIFIC IMMUNOTHERAPY BY INTRODUCING IL-4P INHIBITOR
Heck et al. Pharmacological therapy of bronchial asthma: the role of biologicals
PL213215B1 (en) Low dose methods for treating disorders in which tnf ó activity is detrimental
KR20230130681A (en) Method of treating peanut allergy by administration of IL-4R antagonist and method of strengthening peanut allergen-specific immunotherapy
KR20230164197A (en) Treatment and inhibition of inflammatory lung diseases in patients having risk alleles in the genes encoding il33 and il1rl1
JP2025032243A (en) Bispecific antibodies for use in the treatment of hidradenitis suppurativa - Patent Application 20070233334
JP6663910B2 (en) Method for treating psoriatic patients receiving anti-TNF-α antibody therapy
JPWO2020089473A5 (en)
NZ779309B2 (en) Combination of il-4/il-13 pathway inhibitors and plasma cell ablation for treating allergy
JP2020529434A5 (en)
Dimov et al. Immunomodulators for asthma
NZ772900B2 (en) Anti-fc epsilon-r1 alpha (fcer1a) antibodies, bispecific antigen-binding molecules that bind fcer1a and cd3, and uses thereof
RU2020109331A (en) METHODS FOR TREATMENT OF ACTIVE EOSINOPHILIC ESOPHAGITIS
RU2022119098A (en) METHODS FOR THE TREATMENT OF ACTIVE EOSINOPHILIC ESOPHAGITIS
NZ772900A (en) Anti-fc epsilon-r1 alpha (fcer1a) antibodies, bispecific antigen-binding molecules that bind fcer1a and cd3, and uses thereof